Fall In Systemic Vascular Resistance Research Articles

Cholinergic‐mediated Circulatory Responses at the Onset of Isometric Exercise: Does Sex Matter?

IntroductionWe have shown that handgrip exercise evokes an initial decrease in systemic vascular resistance (SVR), which was abolished by cholinergic blockade (glycopyrrolate) and, thereby, augmented the blood pressure (BP) response. These findings suggest that a cholinergic mechanism is important for the BP and SVR responses at the onset of isometric handgrip exercise in humans. Noteworthy, this previous study included men only, and was not designed to investigate the potential existence of sex‐related differences in immediate BP and circulatory responses evoked at the exercise onset. Given this, the aim of this study was to test the hypothesis that women present an attenuated fall in SVR and increased pressor response compared to men at the onset of isometric handgrip exercise due to a blunted cholinergic vasodilation.MethodsTen healthy men (aged 21 ± 1 year) and 10 women (aged 24 ± 1 year) were recruited. Women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. Participants performed 20s bout of isometric handgrip exercise at 40% of maximal voluntary contraction. Beat‐to‐beat heart rate (HR) (ECG) and mean BP (finger photopletysmography) were continuously measured. Beat‐to‐beat stroke volume (SV) was obtained with the Modelflow method and matched with HR to estimate cardiac output (CO) and SVR. The exercise responses were expressed as a change from 10s immediately before the onset of voluntary contraction.ResultsThe BP response pattern appeared to be different between men and women at the onset of isometric exercise. While men presented a typical exercise‐evoked biphasic BP response (3s: Δ2 ± 2 mmHg; 10s: Δ1 ± 1 mmHg; 20s: Δ5 ± 3 mmHg), women showed a progressive increase in mean BP (3s: Δ1 ± 1 mmHg; 10s; Δ3 ± 1 mmHg; 20s: Δ6 ± 1 mmHg; P=0.681). Men demonstrated a decrease in SVR at 3s (Δ‐0.9 ± 0.3 mmHg.L‐1.min), 10s (Δ ‐1.6 ± 0.4 mmHg.L‐1.min) and 20s (Δ‐1.9 ± 0.7 mmHg.L‐1.min) following the exercise onset, and these responses tended to be attenuated in women (3s: Δ‐0.3 ± 0.3 mmHg.L‐1.min; 10s: Δ‐1.2 ± 0.4 mmHg.L‐1.min; 20s: Δ‐0.6 ± 0.5 mmHg.L‐1.min; P=0.131). There were no sex differences in HR, SV and CO responses to exercise.ConclusionThese findings suggest a lack of sex differences in immediate BP and circulatory responses at the onset of isometric handgrip exercise, indicative of similar cholinergic‐mediated vasodilation in skeletal muscle between men and women.

Fluid challenge and balloon occlusion testing in patients with atrial septal defects

IntroductionCareful, stepwise assessment is required in all patients with atrial septal defect (ASD) to exclude pulmonary vascular or left ventricular (LV) disease. Fluid challenge and balloon occlusion may unmask LV...

Epiural anaesthesia: Superior modality of treatment in lower segment caesarean section in a patient with supracardiac TAPVC

Background: Total Anomalous Pulmonary Venous Connection (TAPVC) is congenital heart disease in which the pulmonary veins do not connect normally to left atrium. Instead they connect to right atrium, often by way of systemic vein. There may be associated cardiac malposition. Anaesthetic management requires detailed assessment of cardiac an extracardiac anomalies & its pathophysiological effects. Here we report a case of TAPVC posted for LSCS and its successful management. Case Presentation: 25yrs female known case of TAPVC at 34.5 wks of gestation admitted 3 weeks prior, Vitaly stable, we did this patient under plain epidural anaesthesia without haemodynamic instability. Conclusions: Epidural anaesthesia a better technique than general anaesthesia for supracardiac TAPVC posted for LSCS. Meticulous intraoperative monitoring is important. Cardiac Output must be maintained, avoid fall in Systemic Vascular Resistance (SVR) ensuring minimal change in shunt. Keywords: Supracardiac TAPVC, LSCS, Epidural Anaesthesia.

Similar Cerebral Blood Flow and Autonomic Responses to Upright Tilt Test in Adult Patients With Different Hemodynamic Mechanisms Leading to Reflex Syncope.

Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope. The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt. At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge. Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

Adenosine, Lidocaine, and Magnesium Support a High Flow, Hypotensive, Vasodilatory State With Improved Oxygen Delivery and Cerebral Protection in a Pig Model of Noncompressible Hemorrhage

BackgroundNoncompressible hemorrhage is the leading cause of preventable death in military and civilian trauma. Our aim was to examine the effect of adenosine, lidocaine, and magnesium (Mg2+; ALM) on cardiovascular and cerebral function in a porcine hepatic hemorrhage model. Materials and methodsPigs (59.1 ± 0.34 kg) were anesthetized, instrumented, and randomly assigned into sham (n = 6), saline controls (n = 10) or ALM (n = 10) groups before laparoscopic liver resection. After 30 min, groups received 4 mL/kg 3% NaCl ± ALM bolus (Phase 1) followed 60 min later with 3 mL/kg/h 0.9% NaCl ± ALM drip (4 h; Phase 2), then transfusion. Hemodynamics, carotid artery flow, and intracranial pressure were measured continuously. Microdialysis samples were analyzed for metabolites. ResultsSaline controls had 20% mortality (mean survival time: 307 ± 38 min) with no ALM deaths over 6 h. Bolus administration increased mean arterial pressure (MAP) in both groups, and drip led to further increases to 62 ± 10 mmHg in controls compared with a steady fall to 47 ± 8 mmHg in ALM group at 240 min. The lower MAP was associated with a dramatic fall in systemic vascular resistance and improved oxygen delivery. ALM drip significantly increased cardiac output and stroke volume with lower dP/dtMin, indicating a less stiff heart. ALM drip also significantly decreased cerebral perfusion pressure, reduced cerebral oxygen consumption (28%), and reduced brain glycerol (60%), lactate (47%), and relative expression of hypoxia-inducible factor (38%) compared with saline controls. ConclusionsALM therapy improved cardiac function and oxygen delivery by lowering systemic vascular resistance after noncompressible hemorrhage. ALM also appeared to protect the brain at hypotensive MAPs with significantly lower cerebral perfusion pressure, lower O2 consumption, and significantly lower cortical lactate and glycerol levels compared to saline controls.

Abstract 071: An Attenuated Nocturnal Dip in Systemic Vascular Resistance is Associated With Increased Left Ventricular Mass

Introduction: Previous work from our laboratory has demonstrated that the nocturnal “dip” in blood pressure (BP) is due primarily to a decrease in systemic vascular resistance (SVR), and that nondipping is associated with a blunted nighttime reduction in SVR. In this analysis, we examined the hypothesis that a blunted nocturnal SVR fall is associated with increased LV mass. Methods: 24-hour ambulatory hemodynamics were assessed in a biracial sample of 116 men and women with elevated clinic BP (130-159/80-99 mmHg). Ambulatory BP monitoring was coupled with synchronized measurements of cardiac output by ambulatory impedance cardiography. Values for SVR were derived for each ambulatory BP measurement. Left ventricular (LV) mass was measured by echocardiography and indexed by height 2.7 to adjust for differences in body size. Multivariable regression models were used to examine the relationships between LV mass index and demographic characteristics, anthropomorphic variables, daytime ambulatory systolic BP, and dipping of SVR and systolic BP. Results: The study cohort averaged 45.3 ± 8.3 years of age; 42% (49 of 116) of the subjects were female and 47% (54 of 116) were African American. The mean body mass index (BMI) was 28.3 ± 3.8 kg/m 2 . The mean daytime ambulatory systolic BP was 137 ± 11 mmHg; the systolic BP dip averaged 13 ± 5%, and the nocturnal fall in SVR averaged 13 ± 15%. In a model that included age, sex, race, BMI, and daytime systolic BP, daytime systolic BP was significantly associated with LV mass index (b=0.33, p=0.0004). The SVR percent dip, (b=-0.21, p=0.02) but not the percent dip in systolic BP (b=-0.15, p=0.11), was an independent predictor LV mass index when added to this model. Conclusions: A blunted nocturnal dip in SVR is associated with increased LV mass index, independent of daytime systolic BP. This finding suggests that an attenuated nighttime fall in SVR may contribute to left ventricular hypertrophy.

Initial orthostatic hypotension in teenagers and young adults.

ObjectiveTo assess: (1) the frequency of an abnormally large fall in blood pressure (BP) upon standing from supine in patients with initial orthostatic hypotension (IOH); (2) the underlying hemodynamic mechanisms of this fall in BP upon standing from supine and from squatting.MethodsIn a retrospective study of 371 patients (≤30 years) visiting the syncope unit, the hemodynamic response to standing and squatting were studied in 26 patients who were diagnosed clinically with IOH, based on history taking only. In six patients changes in cardiac output (CO) and systemic vascular resistance (SVR) were determined, and the underlying hemodynamics were analyzed.Results15/26 (58 %) patients with IOH had an abnormally large initial fall in systolic BP (≥40 mmHg). There was a large scatter in CO and SVR response after arising from supine [ΔCO at BP nadir median −8 % (range −37, +27 %); ΔSVR at BP nadir median −31 % (range −46, +10 %)]. The hemodynamic response after squatting showed a more consistent pattern, with a fall in SVR in all six patients [ΔCO at BP nadir median +23 % (range −12, +31 %); ΔSVR at BP nadir median −42 %, (range −52, −35 %)].InterpretationThe clinical diagnosis of IOH is based on history taking, as an abnormally large fall in systolic BP can only be documented in 58 %. For IOH upon standing after supine rest, the hemodynamic mechanism can be either a large fall in CO or in SVR. For IOH upon arising from squatting a large fall in SVR is a consistent finding.

Incremental epidural anaesthesia for emergency caesarean section in a patient with ostium secundum atrial septal defect and severe pulmonary stenosis with right to left shunt.

Sir, Association of atrial septal defect (ASD) and pulmonary stenosis (PS) with bidirectional shunt in pregnancy is a very rare entity. Death can occur anytime during pregnancy or labour in these patients, precipitated by altered cardiovascular physiology of pregnancy.[1] A 25-year-old primi, an unbooked case with 38 weeks of gestation was posted for emergency caesarean section (CS) for cephalopelvic disproportion. In the second trimester, assessment of breathlessness (NYHA Grade III) with two-dimensional echocardiography revealed an ostium secundum type of ASD (8 mm × 10 mm) with predominantly right to left shunt (Qp: Qs - 0.85), severe PS (Maximum velocity [Vmax ]/peak pressure gradient [PGmax ] - 4.8 m/s/70.4 mm Hg), mild tricuspid regurgitation (Vmax /PGmax - 2.7 m/s/30.5 mm Hg), mild pulmonary regurgitation (Vmax /PGmax - 2.1 m/s/17.58 mm Hg), right ventricular hypertrophy (right ventricle diastolic wall thickness 6 mm) and normal biventricular function with ejection fraction of 60%. In the operation room, oxygen saturation (on room air) was 90-95%, pulse rate was 114/min regular and noninvasive blood pressure was 150/90 mmHg. The patient was premedicated with injection ranitidine (50 mg) and injection metoclopramide (10 mg) and colloid was started at 50 ml/h. Injection ceftriaxone 1 g was administered for antibiotic coverage. The initial central venous pressure was 13 cm H2O and was maintained between 12 and 14 cm H2O. Under aseptic precautions, an 18-gauge epidural catheter was inserted at L3 -L4 epidural interspace. A total volume of 20 ml local anaesthetic solution (13 ml of 2% lignocaine with adrenaline (5 μg/ml) and 1 ml of sodium bicarbonate and 1 ml (50 mg) of tramadol diluted with 5 ml saline) was administered through the epidural catheter in 5 ml increments for achieving a block height up to T4 dermatome. At the time of skin incision, injection ketamine (50 mg) and injection midazolam (1 mg) was administered in titrating doses. CS proceeded uneventfully, and a healthy male baby was delivered with Apgar score of 8 and 9 at 1 and 5 min, respectively. A bolus dose of 0.4 mg intravenous methylergometrine was administered slowly, and a slow infusion of oxytocin 10 units was started. The surgery lasted for about 60 min, and the blood loss was 500 ml. A total of 450 ml colloid and 100 ml oxytocin-normal saline infusion was given. Post-operative analgesia was provided with epidural top-up, whenever the patient complained of pain or visual analogue score was ≥4. At 48th h of follow-up, she had maximal scores for post-operative pain relief and overall satisfaction. She was discharged on the 7th post-operative day and referred to cardiology department for further management. The mortality in patients with ASD and severe PS with right to left shunt in pregnancy is unknown,[2] as many unsuccessful cases are not reported. In our case, although the patient was having reversal of shunt, she was asymptomatic and had no signs of chronic cyanosis. This may be due to hyperdynamic circulation of pregnancy producing increased pulmonary gradients and the restrictive ASD causing inadequate mixing of blood to produce clinical cyanosis.[3] Epidural anaesthesia (EA) was planned because of its slower onset and less and delayed haemodynamic variations compared to spinal and combined spinal-epidural technique.[4] General anaesthesia (GA) poses clear risks related to pulmonary vascular resistance and magnitude of the shunt. As the patient was in labour, we had no sufficient time for further cardiac evaluation. Pulse oximeter is used to assess the degree of right to left shunt during the peri-operative period.[5] Our principle was to maintain the cardiac output and to avoid the fall in systemic vascular resistance (SVR). We optimised the SVR based on mean arterial pressure to avoid the increase in shunt magnitude. Oxytocin bolus can cause direct vasodilatation and reduce SVR with a compensatory increase in heart rate and cardiac output in pregnant women. Use of methylergometrine lowered the use of vasoconstrictors[6] and added to haemodynamic stability. Colloids provide greater haemodynamic stability by remaining in the intravascular space for longer time and avoid volume overloading; this helps to decrease the magnitude of shunt and right ventricular failure.[7] The use of lower dose of lignocaine with adrenaline, bicarbonate and tramadol provided a more rapid onset and superior quality block to touch.[8] We did not institute any thromboprophylaxis measures; EA itself can reduce risk of perioperative venous stasis and embolism. To conclude, EA can be safely and effectively used for CS in pregnant patients having pulmonary vascular disease with reversal of shunts provided the SVR is maintained throughout the surgical procedure. Major haemodynamic complications and risk of embolism during GA can be avoided if EA is properly planned and administered. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Incremental epidural anaesthesia for emergency caesarean section in a patient with ostium secundum atrial septal defect and severe pulmonary stenosis with right to left shunt

Sir, Association of atrial septal defect (ASD) and pulmonary stenosis (PS) with bidirectional shunt in pregnancy is a very rare entity. Death can occur anytime during pregnancy or labour in these patients, precipitated by altered cardiovascular physiology of pregnancy.[1] A 25-year-old primi, an unbooked case with 38 weeks of gestation was posted for emergency caesarean section (CS) for cephalopelvic disproportion. In the second trimester, assessment of breathlessness (NYHA Grade III) with two-dimensional echocardiography revealed an ostium secundum type of ASD (8 mm × 10 mm) with predominantly right to left shunt (Qp: Qs - 0.85), severe PS (Maximum velocity [Vmax ]/peak pressure gradient [PGmax ] - 4.8 m/s/70.4 mm Hg), mild tricuspid regurgitation (Vmax /PGmax - 2.7 m/s/30.5 mm Hg), mild pulmonary regurgitation (Vmax /PGmax - 2.1 m/s/17.58 mm Hg), right ventricular hypertrophy (right ventricle diastolic wall thickness 6 mm) and normal biventricular function with ejection fraction of 60%. In the operation room, oxygen saturation (on room air) was 90-95%, pulse rate was 114/min regular and noninvasive blood pressure was 150/90 mmHg. The patient was premedicated with injection ranitidine (50 mg) and injection metoclopramide (10 mg) and colloid was started at 50 ml/h. Injection ceftriaxone 1 g was administered for antibiotic coverage. The initial central venous pressure was 13 cm H2O and was maintained between 12 and 14 cm H2O. Under aseptic precautions, an 18-gauge epidural catheter was inserted at L3 -L4 epidural interspace. A total volume of 20 ml local anaesthetic solution (13 ml of 2% lignocaine with adrenaline (5 μg/ml) and 1 ml of sodium bicarbonate and 1 ml (50 mg) of tramadol diluted with 5 ml saline) was administered through the epidural catheter in 5 ml increments for achieving a block height up to T4 dermatome. At the time of skin incision, injection ketamine (50 mg) and injection midazolam (1 mg) was administered in titrating doses. CS proceeded uneventfully, and a healthy male baby was delivered with Apgar score of 8 and 9 at 1 and 5 min, respectively. A bolus dose of 0.4 mg intravenous methylergometrine was administered slowly, and a slow infusion of oxytocin 10 units was started. The surgery lasted for about 60 min, and the blood loss was 500 ml. A total of 450 ml colloid and 100 ml oxytocin-normal saline infusion was given. Post-operative analgesia was provided with epidural top-up, whenever the patient complained of pain or visual analogue score was ≥4. At 48th h of follow-up, she had maximal scores for post-operative pain relief and overall satisfaction. She was discharged on the 7th post-operative day and referred to cardiology department for further management. The mortality in patients with ASD and severe PS with right to left shunt in pregnancy is unknown,[2] as many unsuccessful cases are not reported. In our case, although the patient was having reversal of shunt, she was asymptomatic and had no signs of chronic cyanosis. This may be due to hyperdynamic circulation of pregnancy producing increased pulmonary gradients and the restrictive ASD causing inadequate mixing of blood to produce clinical cyanosis.[3] Epidural anaesthesia (EA) was planned because of its slower onset and less and delayed haemodynamic variations compared to spinal and combined spinal-epidural technique.[4] General anaesthesia (GA) poses clear risks related to pulmonary vascular resistance and magnitude of the shunt. As the patient was in labour, we had no sufficient time for further cardiac evaluation. Pulse oximeter is used to assess the degree of right to left shunt during the peri-operative period.[5] Our principle was to maintain the cardiac output and to avoid the fall in systemic vascular resistance (SVR). We optimised the SVR based on mean arterial pressure to avoid the increase in shunt magnitude. Oxytocin bolus can cause direct vasodilatation and reduce SVR with a compensatory increase in heart rate and cardiac output in pregnant women. Use of methylergometrine lowered the use of vasoconstrictors[6] and added to haemodynamic stability. Colloids provide greater haemodynamic stability by remaining in the intravascular space for longer time and avoid volume overloading; this helps to decrease the magnitude of shunt and right ventricular failure.[7] The use of lower dose of lignocaine with adrenaline, bicarbonate and tramadol provided a more rapid onset and superior quality block to touch.[8] We did not institute any thromboprophylaxis measures; EA itself can reduce risk of perioperative venous stasis and embolism. To conclude, EA can be safely and effectively used for CS in pregnant patients having pulmonary vascular disease with reversal of shunts provided the SVR is maintained throughout the surgical procedure. Major haemodynamic complications and risk of embolism during GA can be avoided if EA is properly planned and administered. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response of the muscle is relatively small compared with the onset of leg cycling, where a marked increase in muscle blood flow rapidly occurs as a consequence of multiple redundant mechanisms. We recorded blood pressure (BP; brachial artery), stroke volume (pulse contour analysis), cardiac output, and systemic vascular resistance (SVR) in young healthy males, while performing either 20 s of isometric handgrip contraction at 40% maximum voluntary contraction (protocol 1; n = 9) or 20 s of low-intensity leg cycling exercise (protocol 2; n = 8, 42 ± 8 W). Exercise trials were conducted under control (no drug) conditions and following cholinergic blockade (glycopyrrolate). Under control conditions, isometric handgrip elicited an initial increase in BP (+5 ± 2 mmHg at 3 s and +3 ± 1 mmHg at 10 s, P < 0.05), while SVR dropped after 3 s (-27 ± 6% at 20 s; P < 0.05). Cholinergic blockade abolished the isometric handgrip-induced fall in SVR and, thereby, augmented the pressor response (+13 ± 3 mmHg at 10 s; P < 0.05 vs. control). In contrast, cholinergic blockade had a nonsignificant effect on changes in BP and SVR at the onset of leg cycling exercise. These findings suggest that a cholinergic mechanism is important for the BP and SVR responses at the onset of isometric handgrip exercise in humans.

Transversus abdominis plane block as sole anaesthetic technique for inguinal hernia repair in two patients having complex medical conditions

Sir, Transversus abdominis plane (TAP) block has been used as a sole anaesthetic technique for the patients with multiple co-morbidities presenting for emergency laparotomy.[1,2] We share our experience of using TAP block for the surgical anaesthesia in two patients scheduled for inguinal hernioplasty who had associated complex medical conditions. First patient was a 52-year-old male, known case of congenitally corrected transposition of great arteries (CCTGA) associated with severe pulmonary stenosis and a pressure gradient of 64 mm Hg, large non-restrictive ventricular septal defect (VSD) and right ventricular (i.e., physiologic left ventricle) dysfunction. He was stable on treatment with tablet torsemide. Second case was a 54-year-old male known case of Takayasu's arteritis (TA) and hypertension on treatment with tablet metoprolol and losartan. The patient had the history of claudication and weakness of left upper limb. The peripheral pulses in left upper limb were feeble and blood pressure (B.P) was lower compared to right upper limb (112/70 mm Hg vs. 172/73 mm Hg). For surgery, ultrasound guided (USG) TAP block was administered in both cases using in-plane posterior approach with 20 ml of 0.5% bupivacaine and 10 ml of 2% lignocaine. For visceral analgesia, the TAP block was supplemented with infusions of dexmedetomidine at the loading dose of 1 μg/kg over 10 min followed by 0.5-0.6 μg/kg/min infusion and fentanyl at 75-100 μg/h, respectively, in the first and the second case. In the first patient, T10 -L1 dermatomes were blocked whereas in second patient L1 was spared; only T10 -T12 blockade was achieved as checked by pin prick. The incision line was infiltrated with 2% lignocaine in the second case before surgery. The anaesthetic monitoring in both cases included continuous electrocardiogram, continuous invasive B.P monitoring, pulse oximetry, and temperature. The intraoperative vital parameters were stable and surgery was completed uneventfully in both cases. CCTGA is an uncommon congenital cardiac anomaly characterized by TGA along with the inversion of both ventricles and thus there is both atrio-ventricular and ventriculo-great vessel discordance. The anaesthetic haemodynamic goals in these cases are to maintain systemic vascular resistance (SVR) to avoid right to left shunt by VSD and to preserve myocardial contractility.[3] TA involves a focal stenotic process in the aorta and proximal segment of its main branches. In our second case, though angiography was not done, based on the history of claudication and findings of feeble pulses and decreased B.P. in left arm compared to right is suggestive of stenotic area to be in the arch of aorta. These patients may not tolerate the sudden fall in SVR as they have compromised regional circulation and hence similar to the first patient our intraoperative haemodynamic goal was to maintain SVR. We decided to use USG TAP block in both cases as being an abdominal field, it holds the promising advantage of maintaining the haemodynamics of patients, which are altered in general or neuraxial anaesthesia and additionally provides an excellent postoperative analgesia for 24-48 h. We chose dexmedetomidine infusion in the first patient as it has the combination of analgesic, sedative, and anxiolytic properties with the preservation of respiratory functions. There are 3 main issues which need consideration while using TAP block as a sole anaesthetic modality for surgery. First, TAP block covers only the somatic component of surgical pain; for visceral pain analgesia has to be supplemented with other analgesic agents hence it cannot be a sole anaesthetic technique. Second, the extent of dermatomal block provided by TAP block is uncertain. Both pinprick using blunt needle and cold disinfectant swabs can be used to assess dermatomal extent of sensory blockade. Lee et al.[3] reported that posterior approach produced a median sensory block of three dermatomal segments, the most cephalad being T10. We found the L1 dermatome to be spared in the second case despite using 30 ml of drug for block. Since the incision for inguinal hernia repair lies over T12 -L1 segments, additional infiltration of local anaesthetics (L.A) was required before surgery. Niraj et al.[4] also observed that posterior approach TAP block usually spares L1 segment. Another disadvantage of TAP block is potential to produce L.A. toxicity since large volumes of L.A. are used. There are case reports[5] of cardiac arrests due to L.A. systemic toxicity following TAP block. Therefore the volume of drug used should be carefully determined and the patient should be observed for at least 45 min after TAP block institution during intraoperative and postoperative period. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Pulmonary artery wave reflection: observations in pulmonary hypertension

Introduction: PIMR is a novel index of pulmonary microvascular function calculated from PressureWirederived distal pressure and flow. While PIMR has been reported in a large animal model of pulmonary arterial hypertension (PAH), its utility in the clinical setting has not been explored. Methods: Patients referred for diagnostic right heart catheterisation underwent Swan Ganz catheter and PressureWire (placed in 3rd order PA branch) measurement of pulmonary haemodynamics both before and during adenosine infusion. PIMR was calculated as mean transit time× (distal PA pressure−PA wedge pressure). Results: Thirty-eight subjects (average age 61 years) were studied including five normal, eleven PAH, fifteen heart failure with normal ejection fraction (HFNEF), five mitral valve disease, and two interstitial lung disease patients. Adenosine infusion resulted in 28% fall in pulmonary vascular resistance (PVR) and a 29% fall in systemic vascular resistance driven mainly by an increase in cardiac output (5.9± 0.3 L/min vs. 8.6± 0.4 L/min, p< 0.001). PIMR was closely related to PVR during adenosine (r= 0.63, p< 0.001). PIMR was higher in patients with transpulmonary gradient greater than 12 (6.9± 1.3 vs. 3.6± 0.9, p< 0.018) and in patients with PAH compared to those with HFNEF (10.5± 1.7 vs. 3.2± 0.4, p< 0.001). Conclusions: PIMR is closely related to PVR, suggesting that resistance in the pulmonary circulation occurs mainly at the microvascular level. While adenosine is an effective pulmonary vasodilator, its substantial effect on systemic resistance may make alternative agents such as PDE-5 inhibitors more attractive for pulmonary vasodilator challenge.

Pulmonary Wave Reflection: Observations in Pulmonary Hypertension

Introduction: PIMR is a novel index of pulmonary microvascular function calculated from PressureWirederived distal pressure and flow. While PIMR has been reported in a large animal model of pulmonary arterial hypertension (PAH), its utility in the clinical setting has not been explored. Methods: Patients referred for diagnostic right heart catheterisation underwent Swan Ganz catheter and PressureWire (placed in 3rd order PA branch) measurement of pulmonary haemodynamics both before and during adenosine infusion. PIMR was calculated as mean transit time× (distal PA pressure−PA wedge pressure). Results: Thirty-eight subjects (average age 61 years) were studied including five normal, eleven PAH, fifteen heart failure with normal ejection fraction (HFNEF), five mitral valve disease, and two interstitial lung disease patients. Adenosine infusion resulted in 28% fall in pulmonary vascular resistance (PVR) and a 29% fall in systemic vascular resistance driven mainly by an increase in cardiac output (5.9± 0.3 L/min vs. 8.6± 0.4 L/min, p< 0.001). PIMR was closely related to PVR during adenosine (r= 0.63, p< 0.001). PIMR was higher in patients with transpulmonary gradient greater than 12 (6.9± 1.3 vs. 3.6± 0.9, p< 0.018) and in patients with PAH compared to those with HFNEF (10.5± 1.7 vs. 3.2± 0.4, p< 0.001). Conclusions: PIMR is closely related to PVR, suggesting that resistance in the pulmonary circulation occurs mainly at the microvascular level. While adenosine is an effective pulmonary vasodilator, its substantial effect on systemic resistance may make alternative agents such as PDE-5 inhibitors more attractive for pulmonary vasodilator challenge.

120: Effects of spinal anaesthesia on left ventricular function assessed by two-dimensional echocardiography

Spinal anaesthesia (SA) is one of the most frequently realized techniques of regional anaesthesia to allow lower limbs surgery. Hypotension is an adverse effect commonly observed, especially in elderly patients. Indeed the sympathetic block induced by SA decreases left ventricular (LV) preload and afterload, the cardiac effect of SA is still controversial. The aim of this study was to compare the effect of SA and general anesthesia (GA) on left ventricular systolic function assessed by 2D strain by transthoracic echocardiography (TTE). During 6 months, 22 patients over 60 years old referred for elective lower limb surgery underwent TTE immediately before and 15 minutes after SA (n= 10) or GA (n= 12). Hypotension was more frequent in the GA group than in the SA group (83% vs. 16%, P =0.008). The use of fluid expansion and vasopressors was higher in the GA group (P =0.03). GA and SA induced both a significative increase of global longitudinal strain rate (−0.2 ±0.3%.s-1 vs. −0.2 ±0.3%.s-1 respectively; P [GA vs. SA]= ns). LV ejection fraction and LV telediastolic volume were not modified by both anesthesia. Systolic peak velocities at the mitral annulus by tissue Doppler imaging was increased by SA but not by GA (respectively +1.2 cm. s-1; P= 0.026 vs. −0.4 cm. s-1; P= 0.5). Diastolic function was modified by GA (E/A ratio = 1.1 ±0.3 vs. 1.2 ±0.4; P= 0.05) but not by SA (E/A ratio= 0.9 ±0.3 vs. 0.9 ±0.4; P= 0.24). All these effects lead to a decrease of aortic velocity time integral in the GA group contrary to in the SA group (−1.1 ±7.4 P= 0.02 for GA vs. −0.38 ±3.85, P= 0.8 for SA). Both SA and GA induce increase of LV global longitudinal strain rate and systolic peak velocity. During GA, these adaptations of systolic function are not enough to compensate the fall of systemic vascular resistance and lead to more hypotension than during SA. These results encourage privileging SA in patients without myocardial reserve, especially older patients.

Pulmonary Index of Microvascular Resistance (PIMR) using PressureWire: First Report in 38 Human Subjects

Introduction: PIMR is a novel index of pulmonary microvascular function calculated from PressureWire-derived distal pressure and flow. While PIMR has been reported in a large animal model of pulmonary arterial hypertension (PAH), its utility in the clinical setting has not been explored. Methods: Patients referred for diagnostic right heart catheterisation underwent Swan Ganz catheter and PressureWire (placed in 3rd order PA branch) measurement of pulmonary haemodynamics both before and during adenosine infusion. PIMR was calculated as mean transit time × (distal PA pressure − PA wedge pressure). Results: Thirty-eight subjects (average age 61 years) were studied including five normal, eleven PAH, fifteen heart failure with normal ejection fraction (HFNEF), five mitral valve disease, and two interstitial lung disease patients. Adenosine infusion resulted in 28% fall in pulmonary vascular resistance (PVR) and a 29% fall in systemic vascular resistance driven mainly by an increase in cardiac output (5.9 ± 0.3 L/min vs. 8.6 ± 0.4 L/min, p < 0.001). PIMR was closely related to PVR during adenosine (r = 0.63, p < 0.001). PIMR was higher in patients with transpulmonary gradient greater than 12 (6.9 ± 1.3 vs. 3.6 ± 0.9, p < 0.018) and in patients with PAH compared to those with HFNEF (10.5 ± 1.7 vs. 3.2 ± 0.4, p < 0.001). Conclusions: PIMR is closely related to PVR, suggesting that resistance in the pulmonary circulation occurs mainly at the microvascular level. While adenosine is an effective pulmonary vasodilator, its substantial effect on systemic resistance may make alternative agents such as PDE-5 inhibitors more attractive for pulmonary vasodilator challenge.

Georg Ohm and the Changing Character of Aortic Stenosis

Severe aortic stenosis (AS) untreated by aortic valve replacement is a fatal disease with a 3-year mortality rate of 75% once the classic symptoms of the disease ensue.1–4 Approximately 15% of AS patients present with syncope, which is an ominous occurrence.2 Indeed, a master cardiologist and my former mentor, Dr Lewis Dexter, quipped that sudden death in AS was simply prolonged syncope. Although exercise-induced arrhythmia and/or a pressure-induced vasodepressor response have been invoked to explain syncope in AS, the most commonly held theory invokes Ohm's law. This well-known principle states that V=I×R, where V is voltage, I is current, and R is resistance. Applied to the circulation, the terms are substituted such that P=CO×R, where P is pressure, CO is cardiac output (L/min), and R is the vascular resistance in the area of interest. The Figure diagrams the circulation in the patient with AS as having 3 major resistors: R1, the total pulmonary resistance made up of left ventricular (LV) filling pressure plus pulmonary vascular resistance that governs LV filling; R2, the resistance offered by the aortic valve; and R3, the systemic vascular resistance (SVR). Pressure at these 3 points in the circulation is determined by the product of CO×R. If resistance drops without a concomitant increase in output, pressure must also fall. In severe AS, it has been assumed that R2 (valve resistance) exceeds R3 (SVR) substantially. As such, a fall in SVR caused by exercise or by administration of a vasodilator would cause a fall in systemic pressure because R2, the severely stenotic aortic valve, would block a compensatory increase in forward output causing systemic hypotension and syncope. Is this theory proven? Article see p 2353 Figure. Diagram of the circulation as an electric circuit. …

Reversal of Heparin by Novel Synthetic Antagonist PMX-60056 Exhibits a Linear Dose-Response Relationship

AbstractAbstract 3329PMX-60056 is a small-molecule first-in-class new chemical entity designed to bind to the pentasaccharide group in unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), and reverse their anticoagulation effects. It has been shown to reverse UFH and the LMWH tinzaparin to date, and without rebound anticoagulation.When no UFH or LMWH is present, PMX-60056 dosing has been limited by transient hypotension at doses over 0.4 mg/kg in volunteers, but its use for heparin reversal should eliminate this effect as PMX-60056 preferentially binds to heparin. A study with UFH at 70 U/kg and reversal with 0.3 mg/kg PMX-60056 showed full efficacy, and mild blood-pressure reductions in half the subjects that suggested excess PMX-60056.Therefore, we examined the dose-response, efficacy, and safety at higher doses of UFH as used in cardiac surgery. Hemodynamic effects were recorded with lithium-dilution cardiac output, and blood pressures were continuous intra-arterial measurements. PMX-60056 dose was titrated using activated clotting times (ACTs), and protamine requirements were also estimated by heparin-protamine titrations to determine heparin levels.350 U/kg of heparin was reversed in 6 normal volunteers, after an initial 10-minute infusion of 0.7 mg/kg PMX-60056 and subsequent smaller doses as needed to normalize ACT. Hemodynamics were unaffected until total PMX-60056 dose exceeded 1 mg/kg – the initial dose of 0.7 mg/kg never produced a change. When a hemodynamic effect did occur (in 3 of the 6), it was initiated by a fall in systemic vascular resistance. Only 1 of these 6 subjects had a clinically significant hypotension, which lasted 15 minutes with pressor agents and limb elevation; this subject was subsequently found to have a past history suggestive of vaso-vagal instability. The other 5 subjects had no appreciable change in blood pressure.Per protocol the antagonist doses were in discrete amounts, so some overshoot was inevitable. Therefore, the total dose of PMX-60056 to the point immediately preceding full reversal of ACT was correlated with ACT, with initial protamine requirement according to heparin levels, and with estimated residual heparin (calculated from dose given and time elapsed). These data were highly correlated with a straight line from zero: R-squared was 0.90 with initial ACT, 0.96 with initial protamine requirement according to heparin levels, and 0.97 with estimated residual heparin (calculated).These data suggest that measurements routinely available during cardiac surgery are sufficient for predicting a single reversing dose of PMX-60056 that will safely and effectively neutralize UFH-induced anticoagulation.After reversal, the ability to re-anticoagulate is sometimes important. The same study also established that reversal of anticoagulation with PMX-60056 did not inhibit subsequent repeat anticoagulation with heparin a few minutes later, which was then also reversed with PMX-60056.This study was conducted according to cGCP at Duke University's Anesthesiology Research Unit. More results will be forthcoming as the analysis proceeds. Disclosures:McAllister:PolyMedix, Inc.: Employment.

Exercise Testing and Training in Children With Congenital Heart Disease

The primary function of the cardiopulmonary system is to provide blood flow (and oxygen) in quantities sufficient to support the metabolic needs of the body. The capacity of the cardiopulmonary system to fulfill this function is maximally stressed when an individual's metabolic rate is increased, a condition that occurs most commonly during physical activity/exercise. A number of physiological changes accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise (Figure 1). In normal individuals, these changes (which during upright exercise include a tripling of the resting heart rate, a >60% reduction in systemic and pulmonary vascular resistance, and a >50% increase in stroke volume) can ultimately produce a >5-fold increase in cardiac output. The increase in cardiac output is accompanied by enhanced ventricular preload (as the ventricles move up their Starling curves to accommodate the increased workload), a doubling of systolic and mean pulmonary artery pressures (most of the increase in pulmonary artery pressures is due to the concomitant rise in left-sided filling pressures; the increase in transpulmonary pressure gradient is relatively small), and a more modest increase in systemic arterial pressures.1,–,4 Figure 1. Some of the physiological changes that accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise. RAp indicates right atrial pressure; LAp, left atrial pressure; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; PAp, pulmonary artery pressure; and AOp, aortic pressure. Congenital heart disease (CHD) may, in a variety of ways and to a variable extent, adversely affect these hemodynamic adaptations. For instance, patients with a Fontan procedure lack a pulmonary ventricle. They therefore cannot increase their pulmonary blood flow and pressures normally (and consequently cannot maintain their ventricular preload and systemic blood flow) during exercise.5 Patients with tetralogy of Fallot and …

Cardiovascular disease in pregnancy

Cardiac disease continues to be an important cause of maternal morbidity and mortality and is now the leading cause of maternal deaths in the United Kingdom. This is largely because of extensive haemodynamic changes which occur during pregnancy, namely the increase in blood volume, fluctuations in cardiac output, fall in systemic vascular resistance and hypercoagulable state. High risk periods include the end of the second trimester, during labour and the immediate postpartum period. Prognosis depends on the specific cardiac condition, the patient's functional class, presence of cyanosis, prior history of cardiac events or arrhythmia and the degree of systolic dysfunction. Conditions where pregnancy should be include Eisenmenger's syndrome, pulmonary hypertension, complex cyanotic congenital heart disease, Marfan syndrome with aortic root dilatation and those with severe left ventricular dysfunction. Women with heart disease should be thoroughly evaluated and counselled before and during pregnancy. Multidisciplinary care is essential for successful maternal and foetal outcomes.

ROLE OF NEURONAL NITRIC OXIDE SYNTHASE IN OVINE SEPSIS MODEL

Smoke inhalation injury is often complicated with pneumonia, which frequently leads to subsequent development of sepsis. Excessive NO has been shown to mediate many sepsis-related pathological responses. In the present study, we used our well-established ovine smoke inhalation and pneumonia/sepsis model to examine the hypothesis that neuronal NO synthase (NOS) may be primarily responsible for these pathological alterations. We report the beneficial effects of the specific neuronal NOS (nNOS) inhibitor ZK234238. Adult female sheep were surgically prepared for the study. After 5 to 7 days' recovery, sheep were anesthetized and given double injury: insufflation of 48 breaths of cotton smoke (<40 degrees C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa (5 x 10(11) colony-forming units) into each sheep's lung via tracheostomy tube. All sheep were mechanically ventilated and fluid resuscitated by lactated Ringer's solution. Sheep were randomly allocated into groups: control (injured not treated, n = 6) and treated (injured, but treated with ZK234238, n = 4). Continuous infusion of ZK234238 (100 microg x kg(-1) x h(-1)) was started 1 h after insult. ZK234238 attenuated the hypotension (at 18 and 24 h) and fall in systemic vascular resistance (at 24 h) seen in control animals. ZK234238 significantly inhibited increased fluid accumulation as well as increased plasma nitrate/nitrite 24 h after injury. Neuronal NOS inhibition significantly reduced lung water content and attenuated inflammatory indices such as lung tissue myeloperoxidase activity, IL-6 mRNA, and reactive nitrogen species. The above results suggest that the nNOS-derived NO may be involved in the pathophysiology of sepsis-related multiorgan dysfunction.