Reduction In Systemic Vascular Resistance Research Articles

The Effects of Dobutamine in Septic Shock: An Updated Narrative Review of Clinical and Experimental Studies.

The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

Factors leading to supranormal cardiac index in pediatric pulmonary hypertension patients treated with parenteral prostanoid therapy.

Parenteral prostanoid therapy (PPT) can result in supranormal cardiac index (SCI; >4 L/min/m2) in pediatric pulmonary hypertension (PPH) patients. We evaluated the incidence, hemodynamic factors, and outcomes associated with SCI in PPH. This retrospective cohort study included 22 PPH patients on PPT from 2005 to 2020. Hemodynamic profiles were compared between the baseline and 3-6 month follow-up catheterization in the SCI and non-SCI cohorts. Cox regression analysis examined time to composite adverse outcome (CAO; Potts shunt, lung transplant, or death) controlling for initial disease severity. SCI developed in 17 (77%) patients, of whom 11 (65%) developed SCI within 6 months. The SCI cohort was characterized by significant augmentation of cardiac index (CI) and stroke volume (SV) as well as reductions in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). Conversely, the non-SCI cohort had unchanged SV despite a modest rise in CI as well as persistent vasoconstriction. After median follow-up of 4.3 years (range 0.2-13 years), non-SCI patients were at significantly increased risk for the CAO (5/5: three deaths, two Potts shunts) compared withSCI patients (5/17: two deaths, three lung transplants; adjusted hazard ratio 14.0 [95% confidence interval: 2.1-91.3], p < 0.001). A majority of PPH patients developed SCI within 6-12 months of starting PPT and demonstrated lower risk of adverse outcomes compared withnon-SCI patients. These data suggest that change in SVR and SV after 3-6 months of PPT may be early markers of therapeutic response and prognosis.

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients.

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

Inspiratory resistance training transiently improves endothelium-dependent dilation in young adults

Introduction: Inspiratory resistance training (IRT) is a resisted breathing exercise originally devised to improve diaphragmatic strength. We have shown IRT to be a potent non-pharmacological therapy that yields significant reductions in resting blood pressure. When performed daily for 6 weeks, systolic blood pressure is reduced by ~9 mmHg, secondary to reductions in systemic vascular resistance. Whereas the effects of IRT on the vasculature have been described over the intermediate term, the acute responses that mediate these longer-term adaptations have not been fully characterized. Purpose: Our primary aim was to quantify the acute effects of a single bout of IRT on (endothelium-dependent dilation) EDD in healthy men and women. Secondarily, our goal was to determine the acute effects of IRT on arterial stiffness. Methods: Nitric oxide-mediated EDD and ischemia-induced maximal shear rate were assessed with brachial artery flow-mediated dilation (FMD), and arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV). Twenty healthy young adults (22.9 ± 3.4 years; 10 males, 10 females) were randomized to the experimental (IRT; 5 sets of 6 breaths at 50% of maximal inspiratory pressure with 1-minute rest intervals) and control (time-matched supine rest) conditions in a crossover design, with at least 48 hours between visits. FMD and PWV were performed before, 10 minutes after, and 40 minutes after the assigned intervention. Statistical analysis included repeated measures ANOVA with Sidak post hoc analyses. Results: All values are mean difference ± SD. There were no between-day differences in EDD at baseline (mean difference: 0.08 ± 3.03%; p=0.908). EDD was significantly increased from baseline at 10 minutes post-IRT (+1.86 ± 2.75%; p=0.025), but returned to baseline levels at 40 minutes post-IRT (-0.10 ± 3.00%; p=0.998). During the control condition, EDD was unchanged from baseline at 10 minutes post-rest and 40 minutes post-rest ( p=0.136). Lastly, maximal shear rate following 5 minutes of forearm blood flow occlusion was not different from baseline at any time point following IRT ( p=0.749) and thus, the change in EDD is not a result of a modified hyperemic response. However, in the control condition maximal shear rate was significantly lower at 40 minutes post-rest, relative to baseline (mean difference -9.94 ± 2.64 per second; p=0.005), although the reduced shear rate did not impact EDD at 40 minutes post-rest. Arterial stiffness was unchanged from baseline in response to IRT ( p=0.217) or the rest intervention ( p=0.150). Conclusions: In healthy young adult men and women, a single bout of IRT elicits a transient enhancement in EDD. The effect endures for at least 10 minutes but is extinguished at 40 minutes post IRT. Repeated acute enhancements in EDD may contribute to sustained IRT-related reductions in vascular resistance after 6 weeks of traini This work was supported by NIA/NIH Grant Number: 1R01AG065346-01A1 (EFB), NIH Training Grant Number: 5T32HL007249-44 (DT), and NIH/NHLBI Grant Number: 1K01HL153326-01 (DHC) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pregnancy-associated aortopathy and sudden postpartum death

A 39-year-old woman who had undergone an uncomplicated elective cesarean section for a low-lying placenta collapsed and died the following day. At autopsy, there was dissection of an aneurysmally-dilated thoracic aorta with 400 mls of fluid and clotted blood in the pericardial sac. There were no features of Marfan syndrome or other connective tissue disorders. Histology revealed thinning of the aortic wall with fragmentation of elastic fibers and no inflammation. Vessels elsewhere were normal. This case demonstrates a rare complication of pregnancy that may not present until after delivery with unexpected collapse and sudden death. Predisposing factors include an increased cardiac output, reduction in systemic vascular resistance, an increase in left ventricular muscle mass, and alterations in serum progesterone and estrogen levels which may cause structural changes to the aortic wall. The possibility of syndromic and familial connective tissue disorders should also be considered.

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by &gt;30% or a MAP &lt;65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

Monitoring haemodynamic changes during transjugular portosystemic shunt insertion with electric cardiometry in sedated and spontaneous breathing patients. A diagnostic test accuracy study.

Transjugular intrahepatic portosystemic shunt (TIPS) allows a high blood volume into systemic circulation abruptly. The primary aim of the study was to investigate the effect of TIPS on systemic, portal hemodynamics, and electric cardiometry (EC) parameters in sedated and spontaneous breathing patients. Secondary aims?? Adult consecutive hepatic patients scheduled for elective TIPS were included. Patients were sedated with bispectral index-guided propofol infusion + fentanyl boluses. EC parameters, i.e., cardiac output (CO) and systemic vascular resistance (SVR) were noted. Noninvasive blood pressure, heart rate, central venous pressure (CVP, cmH2O), and portal venous pressure (PVP, cmH2O) were measured pre- and post-TIPS. Thirty-six people were enrolled (n = 25 included) from Aug 2018 to Dec 2019. Data (expressed in median (IQ)) were: age 33 (27-40) years, body mass index 24 (22.0-27) kg/m2, child A 60%, B 36%, and C 4%. Post-TIPS, PVP decreased (from 40 [37-45] to 34 [27-37] mmHg, P < 0.001), whereas CVP increased (from 7 [4-10] to 16 [10.0-19.0] mmHg, P < 0.001). The CO increased (P = 0.03) and SVR reduced (P = 0.012). The reduction in PVP following successful TIPS insertion elevated the CVP abruptly. EC was able to monitor an immediate increase in the CO and a reduction in SVR in association with the above PVP and CVP changes. The results of this unique study indicate that EC monitoring is promising; however, further evaluation in a larger population and in correlation with other gold-standard CO monitors is still indicated.

Dopamine Adjustment Difficulties in Special Pathophysiological Conditions

Dopamine is a commonly used drug but its biology and cellular action is not well known, its bizarre actions in neonates back to different pattern of receptors on vascular and metabolic excretion rate especially in preterm babies.[1] Dopamine’s physiological action is dose dependent and give maximum diuresis and natriuresis at the dose of 2 micrograms/kg/min compared to 4 micrograms/ kg/min in neonates.[2] Such physiological properties back to immature norepinephrine stores that halt inotropic effects and longer elimination half time related to age that accentuate side effects of dopamine such as tachycardia.[3] Such side effects may accentuate in renal and hepatic deficiency because of lower clearance of dopamine and risk of toxicities in usual doses administration.[4] The other challenging factor for easy administration of dopamine is various inter individual pharmacokinetics property of dopamine especially in seriously ill patients.[5] Cochran study in small sample of selected asphyxiated neonate cases showed low dose dopamine as low as 2.5 micrograms/kg/min cannot decrease mortality and morbidity compared to placebo[6] and doses as low as 7 micrograms/kg/min make pulmonary vasoconstriction in critically ill case and infusion rate of 5 micrograms/kg/min cannot bring target hemodynamic indices in a great proportion of patients (9 of 25) inspite of tachycardia occurred in them as a side effect without increase in stroke volume and modest reduction in systemic vascular resistance.[7-8] Dopamine, efficacy, decrement during lactic acidosis is another challenge in spite of the plasma norepinephrine level was elevated dramatically during severe lactic acid acidosis in compared to normal acidosis.[9]

Effects of Acute Hypobaric Hypoxia Exposure on Cardiovascular Function in Unacclimatized Healthy Subjects: A "Rapid Ascent" Hypobaric Chamber Study.

Background: This study aimed to observe the effects of a fast acute ascent to simulated high altitudes on cardiovascular function both in the main arteries and in peripheral circulation. Methods: We examined 17 healthy volunteers, between 18 and 50 years old, at sea level, at 3842 m of hypobaric hypoxia and after return to sea level. Cardiac output (CO) was measured with Doppler transthoracic echocardiography. Oxygen delivery was estimated as the product of CO and peripheral oxygen saturation (SpO2). The brachial artery’s flow-mediated dilation (FMD) was measured with the ultrasound method. Post-occlusion reactive hyperemia (PORH) was assessed by digital plethysmography. Results: During altitude stay, peripheral oxygen saturation decreased (84.9 ± 4.2% of pre-ascent values; p < 0.001). None of the volunteers presented any hypoxia-related symptoms. Nevertheless, an increase in cardiac output (143.2 ± 36.2% of pre-ascent values, p < 0.001) and oxygen delivery index (120.6 ± 28.4% of pre-ascent values; p > 0.05) was observed. FMD decreased (97.3 ± 4.5% of pre-ascent values; p < 0.05) and PORH did not change throughout the whole experiment. Τhe observed changes disappeared after return to sea level, and normoxia re-ensued. Conclusions: Acute exposure to hypobaric hypoxia resulted in decreased oxygen saturation and increased compensatory heart rate, cardiac output and oxygen delivery. Pre-occlusion vascular diameters increase probably due to the reduction in systemic vascular resistance preventing flow-mediated dilation from increasing. Mean Arterial Pressure possibly decrease for the same reason without altering post-occlusive reactive hyperemia throughout the whole experiment, which shows that compensation mechanisms that increase oxygen delivery are effective.

Clinical Update on Vasopressors and Titration Strategies.

Clinical Update on Vasopressors and Titration Strategies.

Causes of arterial hypotension during anesthetic induction with propofol investigated with perfusion index and ClearSightTM in young and elderly patients.

Mechanism underlying the hypotension during anesthetic induction in elderly patients is inferred to differ from that in younger patients due to structural changes in arteries. The aim of the study was to determine if a decrease in cardiac output (CO) or systemic vascular resistance (SVR) is the main mechanism of the hypotension. Fifty-six patients comprising 28 healthy elderly patients aged 75-90 years (group E) and 28 healthy younger patients aged 20-40 years (group Y) were enrolled. General anesthesia was induced with propofol (1.2 mg/kg, group E; 2 mg/kg, group Y), remifentanil (0.15 µg/kg/min, group E; 0.3 µg/kg/min, group Y) and rocuronium. Primary outcome was to compare serial changes in PI of Radical-7TM, SVR, CO and stroke volume variations (SVV) of ClearSightTM (Edwards Lifesciences Corp., Irvine, CA, USA) during the five-minute period from propofol administration until intubation. The degree of increase in PI and reduction in SVR in group Y were significantly greater than those in group E (P<0.01 with repeated measure ANOVA). The degree of reduction in CO and increase in SVV were significantly larger in group E (P<0.01). All values of mean arterial blood pressure measured during the five-minute correlated negatively with PI in group Y (r=0.44, P<0.01) and positively with CO in group E (r=0.4, P<0.01). The main mechanisms of hypotension during anesthetic induction contribute to the decrease in CO in elderly and reduction of SVR in younger. PI only shows the vascular tone of a finger but can be a surrogate for SVR.

Outcome of Petrosal Venous Sampling in Consecutive 68 Patients From a Major Neurosurgical Center in the United Kingdom

Background: Cushing’s disease is a challenging endocrine disorder caused by non-physiological cortisol excess from adrenocorticotropic hormone (ACTH) secreting pituitary adenoma. Inferior petrosal venous sampling (IPSS) is considered the gold standard investigation to differentiate Cushing’s disease from ectopic ACTH syndrome. Methods: This retrospective study included all patients who underwent IPSS between January 2011 and October 2020 at The National Hospital for Neurology and Neurosurgery in London. Patients demographics, radiological, surgical, endocrinological and, histological data were retrieved. We assessed the accuracy of IPSS in localizing ACTH secreting pituitary adenoma and its concordance with neuroimaging and surgical findings at the time of tumor resection. Results: In total 68 patients underwent IPSS, 22 males and 46 females. The median age was 42 years. IPSS was performed prior to primary surgery in 61 patients (90%) and before secondary surgery in 4 patients (6%). Three patients (4%) are awaiting surgery at the time of our study. Fifty-two patients (80%) had positive histology of ACTH expressing adenoma. Four patients (8%) had ectopic ACTH syndrome. The sensitivity of IPSS in predicting Cushing’s disease prior to corticotropin-releasing hormone (CRH) stimulation was 91% (95% CI [83% to 97%]) and accuracy of 88% (95% CI [77% to 95%]). The sensitivity of IPSS post CRH administration was 96% (95% CI [87% to 100%]) with accuracy of 86% (95% CI [75% to 93%]). Data on lateralization of pituitary adenoma were available for 63 patients. Prior to CRH stimulation, lateralization was right sided in 35 patients (56%), left sided in 15 (24%), and 13 patients (20%) did not have adequate interpetrosal sinus ACTH ratio. Lateralization post CRH stimulation was right sided in 40 patients (64%), left sided in 20 (32%), and 3 patients (4%) did not achieve adequate ACTH gradient ratio between two sides. Eighteen patients (30%) switched adenoma lateralization between pre and post CRH stimulation. Post CRH IPSS was consistent with neuroradiology in localizing pituitary adenomas in 59% (29 out of 49 patients) and concordant with surgical findings in 41% (25 out of 61 patients). Patients with ectopic ACTH syndrome had negative IPSS at all stages. IPSS procedure failed in 2 patients (3%). No post procedure complications were reported. Conclusion: IPSS has high sensitivity in diagnosing pituitary driven Cushing’s disease with good safety profile. However, the reliability in lateralizing pituitary adenoma is debated. One third of patients in this cohort switched lateralization before and after CRH administration. Studies on monkeys and rats showed that CRH induces coronary vasodilation and reduction in systemic vascular resistance.This suggest that CRH might have vasoactive effect on pituitary blood vessels with subsequent influence on IPS:P ACTH gradient ratio between the two sides.

Underlying Causes of High Output Heart Failure

In the U.S., each year, there are more than 500,000 new cases of all types of heart failure. With high output cardiac failure, there is an elevated cardiac output associated with several conditions and diseases, including obesity, chronic anemia, systemic arterio-venous fistula, hypercapnia, mitochondrial dysfunction, and hyperthyroidism. The underlying pathophysiologic mechanisms relate to a reduction in systemic vascular resistance from arterio-venous shunting or peripheral vasodilation. Often there is a decrease in systemic arterial blood pressure and neurohormonal activation leading to heart failure symptoms of dyspnea and fatigue. In a persistent high output state, patients may experience tachycardia, valvular abnormalities, and ventricular dilatation and/or hypertrophy. In this article, there is a review of high output heart failure, including the prevalence, pathophysiology, and common clinical causes of this disease.

Chlorthalidone or Hydrochlorothiazide for Treatment of Hypertension

Chlorthalidone or Hydrochlorothiazide for Treatment of Hypertension

SAT-508 Oh My Thyrotoxic Heart! An Uncommon Presentation of High Output Heart Failure

High output heart failure is an extremely rare manifestation of thyrotoxicosis in patients without heart disease. Thyroid hormone has a potent metabolic, vascular, positive chronotropic and inotropic effects. Thyrotoxicosis is accompanied by a reduction in systemic vascular resistance and an obligatory increase in cardiac output to compensate high metabolic state. Most of the patients had completed or near completed recovery of cardiac function after treatment to euthyroid status, if cut in time.Case of 70 y/o female with past medical history of hypothyroidism, hypertension and chronic smoker, came to emergency room due to lightheadedness, weakness, shortness of breath, palpitations and acute bedridden for one week ago. Denied fever, nausea, vomiting or chest pain. On examination patient presented with 122bpm, 23rpm and normotensive. She was in acute respiratory distress requiring BiPAP. Lungs auscultation bilateral crackles, decrease sounds in the bases. Cardiac exam significant for tachycardia, lower extremity edema and JVD +. Laboratories significant for CKD stage 2, chronic anemia and hypoxemia. EKG no ST changes neither T depressions. CXR day #1 reported no cardiopulmonary disease. Basing in these she was admitted with Suspected Pulmonary Embolism. Well’s score was moderate risk; a Chest CTA and full anticoagulation were ordered. Later, venous duplex reported no DVT and D-dimer levels 1.65μg/ml. TSH levels significant decrease 0.0002mU/L and T4 1.800ng/dL. CXR Day#2 reported pulmonary edema and pleural effusion. ECHO2D moderate LVH and preserved systolic function. Patient referred her doctor recently increased thyroid medications from 50 to 100 mcg. Instead of presenting with pulmonary embolism, she has hyperthyroidal state causing cardiac failure. Levothyroxine, heparin and Chest CTA scan were cancelled. She was started in Atenolol and diuretics. Patient symptoms improved and was discharged home to be followed in the clinic. After one week, TSH levels were in 0.008mU/L and one month later in 3.032mU/L. She was started in Levothyroxine 50mcg, to maintain patient euthyroid state.This case illustrates that sometimes tachycardia and tachypnea are symptoms which frequently presents as baffling diagnostic problems. The association of thyrotoxicosis and cardiovascular morbidity is well established. Thyrotoxicosis most common cardiac manifestation is high output heart failure. Patients presenting with heart failure may have thyrotoxicosis as the underlying cause. Treatment of the thyrotoxicosis can restore normal heart function. Hyperthyroidal state may be take into consideration as a differential of tachycardia and tachypnea even if it’s not one of the common causes. Awareness of this presentation may help identify patients with reversible dilated cardiomyopathy and other complications.

Heartbeat: bathing daily is associated with a lower cardiovascular risk

Lifestyle behaviours such as smoking, exercise and diet have received consideration attention as risk factors for cardiovascular disease (CVD) with lifestyle modification now serving as the foundation for primary prevention....

The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome.

Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (KATP) channels genes, ABCC9 and KCNJ8, is a characteristic feature of Cantú syndrome (CS). How potassium channel over-activity results in cardiac hypertrophy, as well as the long-term consequences of cardiovascular remodeling in CS, is unknown. Using genome-edited mouse models of CS, we therefore sought to dissect the pathophysiological mechanisms linking KATP channel GoF to cardiac remodeling. We demonstrate that chronic reduction of systemic vascular resistance in CS is accompanied by elevated renin–angiotensin signaling, which drives cardiac enlargement and blood volume expansion. Cardiac enlargement in CS results in elevation of basal cardiac output, which is preserved in aging. However, the cardiac remodeling includes altered gene expression patterns that are associated with pathological hypertrophy and are accompanied by decreased exercise tolerance, suggestive of reduced cardiac reserve. Our results identify a high-output cardiac hypertrophy phenotype in CS which is etiologically and mechanistically distinct from other myocardial hypertrophies, and which exhibits key features of high-output heart failure (HOHF). We propose that CS is a genetically-defined HOHF disorder and that decreased vascular smooth muscle excitability is a novel mechanism for HOHF pathogenesis.

Adenosine as cardioprotective in off-pump coronary artery bypass grafting

ObjectiveTo assess the effect of adenosine as a cardioprotective drug and its role in attenuating ischemia-reperfusion injury during off-pump coronary artery bypass surgery.BackgroundCardioprotective drugs have long been investigated for use during off-pump coronary artery bypass surgery to attenuate ischemia-reperfusion injury and limit hemodynamic instability. Adenosine has been investigated due to its cardioprotective effect that is mediated through A1 and A3 adenosine receptors. Stimulation of these receptors reproduces the infarct-limiting effect of ischemic preconditioning.MethodsAfter approval of the local ethics committee and informed written consent, fifty patients undergoing elective off-pump coronary artery bypass grafting were prospectively studied. The adenosine group received an infusion of Adenoscan at a rate of 50 μg/kg/min for 15 min. The control group received normal saline at the same rate and volume calculated. Pulmonary artery catheter was introduced through the right internal jugular vein. Cardiac output measurements were obtained. Cardiac index, stroke volume, systemic vascular resistance, pulmonary vascular resistance, right ventricular stroke work index, and left ventricular stroke work index were derived. Hemodynamic measurements were recorded together with blood levels of troponin I and CK-MB fraction to detect perioperative myocardial necrosis. Postoperative duration of mechanical ventilation, ICU stay together with inotropic support quantification using inotropic score were recorded.ResultsFifty patients were included in the study. In the adenosine group, the infusion of adenosine resulted in a significant reduction in mean pulmonary artery pressure after stopping drug infusion (18 ± 2.2 mmHg versus 31 ± 4.1 mmHg). There was a recorded increase in cardiac index in the adenosine group that started 15 min after adenosine infusion and lasted for 12 h postoperatively (p < 0.001). Also, adenosine infusion resulted in a reduction in pulmonary vascular resistance that exceeded the reduction in systemic vascular resistance which resulted in a decrease in pulmonary vascular resistance/systemic vascular resistance ratio (0.14 in adenosine group 15 min after injection versus 0.28 in control group) and (0.11 in adenosine group 12 h postoperatively versus 0.26 in control group). The cTroponin I measured 6 h postoperatively was less in the adenosine group compared with the control group (5.8 ± 2.8 ng/ml versus 16.5 ± 3.9 ng/ml).ConclusionAdenosine infusion during off-pump coronary artery surgery may improve cardiac index, reduce the need for inotropes, and have cardioprotective effect.

Mild Hypobaric Hypoxia Enhances Post-exercise Vascular Responses in Young Male Runners.

It has been reported that sustained post-exercise vasodilation may be linked to exercise-induced angiogenesis. The present study aimed to evaluate whether mild hypobaric hypoxia enhances the post-exercise reduction in systemic vascular resistance in young male runners. Seven male intercollegiate runners (aged 19–21 years) performed maximal incremental treadmill running under conditions of hypobaric hypoxia (corresponding to 2,200 m above sea level, hereinafter referred to as HH) and normobaric normoxia (corresponding to sea level, hereinafter referred to as NN). A third exercise test was performed under NN conditions, consisting of submaximal exercise with the same absolute exercise volume as was achieved during HH (submaximal exercise under NN conditions, hereinafter referred to as NNsubmax). Blood pressure and cardiac output (CO) were measured before and at 15, 30, and 60 (p60) minutes after exercise. Compared with NN, exercise time was shorter in HH and NNsubmax conditions (p < 0.05). Systolic blood pressure and mean blood pressure (MBP) were lower after exercise in HH conditions (p < 0.05). No condition-related differences were found in CO. Total peripheral resistance (TPR, defined as the ratio of MBP to CO) was significantly lower after exercise compared to baseline for all conditions (p < 0.05). However, the decrease in TPR was maintained longer after exercise in HH compared with NN and NNsubmax conditions (p < 0.05). At p60, TPR was lower than baseline for HH conditions (p < 0.05), whereas after exercise in NN, and NNsubmax conditions, TPR recovered to baseline by p60. Decreases in systemic vascular resistance after exercise were maintained longer under mild HH conditions compared with NN despite the lower exercise volume of the former.