Intravenous Administration Of Nitroglycerin Research Articles

ARTERIAL BAROREFLEX FUNCTION IS IMPAIRED DURING THE RECOVERY FROM ACUTE LUNG INJURY IN A BLEOMYCIN-INDUCED RAT LUNG INJURY MODEL

Objective: Acute lung injury (ALI) and its clinical correlate, the acute respiratory distress syndrome (ARDS), results due, in part, to disruption of the normal capillary endothelial barrier and invokes perturbations of ventilatory control. ALI is associated with autonomic dysfunction and cardiac arrhythmias. In a recent study we suggested that rats were susceptible to cardiac arrhythmia even during the recovery from ALI, in part, due to abnormalities in cardiac sympathetic ganglia. On the other hand, if arterial baroreflex function is altered during the recovery of ALI remains unknown. The primary goal of this study was to examine baroreflex function during the recovery stage from ALI in a bleomycin (Bleo)-induced rat ALI model. Design and method: ALI was induced in male SD rats (200-250g) using a single intra-tracheal injection of Bleo (2.5 mg/kg). 4 weeks post Bleo (n = 7) or saline (sham, n = 6), rats were anesthetized with urethane (800 mg/kg ip) and alpha-chloralose (40 mg/kg ip) to measure baroreflex sensitivity. Baroreflex curves were generated by measuring the heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to decreases and increases in mean blood pressure (MAP) by intravenous administration of nitroglycerin (25 μg) followed by phenylephrine (10 μg). Differences between sham and Bleo rats were determined by one-way ANOVA followed by the Tukey post hoc test. Results: Compared to sham rats, there was a significant decrease in the RSNA (117.4±11.6 vs. 77.5±8.9 %baseline, P = 0.018) or HR (147.5±9.7 vs. 75.1±11.3 bpm, P<0.001) range in Bleo rats. Minimum RSNA or HR was also decreased in bleo rats compared to sham rats. There was no significant difference in either the slope coefficient or the blood pressure at the midpoint of the range (BP50) between the two groups. There was a significant decrease in peak slope [or maximum gain (Gainmax) in Bleo rats (MAP-RSNA Gainmax: 3.11±0.27 vs. 1.74±0.31, p = 0.017; MAP-HR Gainmax: 3.57±0.31 vs. 1.21±0.14, p<0.001). Conclusions: Our data demonstrate impaired baroreflex function during the recovery state from ALI. Autonomic dysfunction may also contribute to increased cardiovascular risk during the recovery stage from ALI.

Comprehensive clinical phenotyping of nitroglycerin infusion induced cluster headache attacks.

BackgroundNitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way.MethodsA single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms.ResultsThirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects (U = 15, z = −2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66–100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54–100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31–92%) and 11 out of 12 chronic cluster headache (92%, 73–100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit.ConclusionIntravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.

MPS 13-04 EFFECTS OF VASODILATORS ON THE CARDIO-ANKLE VASCULAR INDEX (CAVI) IN ANESTHETIZED RABBITS

Objective: The arterial stiffness is known to be a good predictor of cardiovascular events in hypertensive patients. Cardio-ankle vascular index (CAVI) has been developed for measurement of vascular stiffness from the aorta to tibial artery, which is clinically utilized for assessing the progress of arteriosclerosis. Our recent study has demonstrated that the CAVI is decreased by a vasodilator affecting conduit and muscular arteries. In this study, we compared acute effects of various types of vasodilators on the CAVI in anesthetized rabbits. Design and Method: New Zealand White rabbits were anesthetized with halothane. For measurements of the heart-ankle pulse wave velocity (haPWV) and CAVI, the signals of electrocardiogram, phonocardiogram and blood pressure were fed to the VaSera system to be automatically calculated from the following well-established basic equation: CAVI = (2ρ/ΔP) × ln(Ps/Pd) × haPWV2, where Ps is systolic blood pressure, Pd is diastolic blood pressure, haPWV is heart-ankle pulse wave velocity, ΔP is Ps–Pd, ρ is blood density. Results: Intravenous administration of nitroglycerin or acetylcholine decreased the CAVI accompanied with hypotensive action and reduction of the haPWV. Intravenous administration of nifedipine, nicardipine or cilnidipine unaffected the CAVI, whereas each drug decreased the blood pressure and haPWV. On the other hand, intravenous administration of nicorandil increased the CAVI but decreased the blood pressure and haPWV. Conclusions: Acute effects on the CAVI were different among the vasodilators examined. Pharmacological properties like nitroglycerin and acetylcholine will be beneficial for the prevention of arteriosclerotic diseases of the large artery.

PP.14.15

Objective: Vasodilators are clinically used in accordance with each pharmacological property. For example, Ca2+ channel blockers are prescribed for patients with hypertension, which dilate arterioles leading to reduction of peripheral vascular resistance. Organic nitrates are used for the treatment of various cardiovascular diseases including angina and heart failure to reduce ventricular preload and afterload, which dilates all segments of the vascular system from large conductance arteries to large veins. Since useful indexes reflecting vascular functions of larger conductance arteries are unavailable using non-invasive methods in contrast to the resistant arteries, we assessed whether the cardio-ankle vascular index (CAVI), established as a marker of arterial stiffness, could reflect different pharmacological actions of nicardipine and nitroglycerin on the systemic vasculature in anesthetized rabbits. Design and method: New Zealand White rabbits were anesthetized with halothane. The CAVI was calculated from the well-established basic equations obtained from the variables of brachial and tibial blood pressure and phonocardiogram. Results: Intravenous administration of nicardipine (1, 3 and 10 μg/kg) decreased the blood pressure, femoral arterial vascular resistance, and heart-ankle pulse wave velocity (haPWV) in a dose-dependent manner. Meanwhile, no significant change was detected in the CAVI at 1 and 3 μg/kg, which reflect the defining feature that CAVI is independent of blood pressure. At the highest dose of 10 μg/kg, the index increased. Intravenous administration of nitroglycerin (2, 4 and 8 μg/kg) also decreased the blood pressure, femoral arterial vascular resistance, and haPWV in a dose-dependent manner. Meanwhile, the CAVI decreased in a dose-dependent manner, which may reflect the pharmacological action that nitroglycerin dilates conductance arteries. Conclusions: These results suggest that CAVI is a useful index that can differentiate pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbit.

Vasospasm or Myocarditis: Cardiac Magnetic Resonance Plays a Decisive Role

A previously healthy 36-year-old male was admitted with acute onset chest pain and elevated levels of cardiac enzymes (CK/MB 248/25ng/dl and TnI 7.16ng/dl). He denied use of cocaine or other illicit drugs. Clinical history was negative for recent flu-like syndrome. Physical examination is unremarkable. ECG showed Q wave in lead III with T wave inversion (Figure 1A). An echocardiogram showed a structurally normal heart with no wall motion abnormalities. He had the abrupt recurrence of severe chest discomfort 12 hours later associated with ST segment elevation in I and aVL (Figure 1B). Symptoms were relieved after administration of intravenous nitroglycerin and ECG changes suddenly resolved. Urgent coronary angiography revealed normal coronary arteries, despite slow flow in the left anterior descending artery. The patient was diagnosed with AMI type 2 secondary to probably coronary artery spasm. Cardiac enzymes peaked at CK/MB 2107/147 and TnI 71. On day 4 a cardiac magnetic resonance (CMR) showed normal first pass and areas of subepicardial contrast enhancement in all segments except in the lateral wall at basal level and septal midventricular consistent with extensive myocarditis (Figure 1C).

22 Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure: Bolus, Drip or Both?

Study Objectives: Small studies suggest benefit when nitroglycerin is administered as an intravenous bolus using higher doses in patients with hypertensive heart failure but clinical experience is limited. We sought to compare outcomes with differing methods of intravenous nitroglycerin administration in patients with acute hypertensive heart failure. Methods: We performed a retrospective cohort study of patients who presented to the emergency department (ED) of an urban, teaching hospital with severe, acute hypertensive heart failure between Jan 2007 and July 2011 and received intravenous nitroglycerin. 3 subgroups were defined: 1) those given nitroglycerin by higher dose (≥ 0.5 mg) bolus alone (higher dose nitroglycerin); 2) those given nitroglycerin by continuous intravenous infusion alone (intravenous nitroglycerin); and 3) those given nitroglycerin by concurrent higher dose bolus and continuous IV infusion (higher dose intravenous nitroglycerin). Baseline and acute treatment data were compiled along with the following outcome measures: use of bilevel positive airway pressure or endotracheal intubation; intensive care unit [ICU] admission rate; ED, ICU and total hospital length of stay; rate of delayed-onset cardiac injury (ie, 2nd but not 1st troponin positive); inhospital mortality; 30-day heart failure readmission rate; and days out-of-hospital and alive through 30-days post-discharge. Descriptive statistics were applied and comparisons using chi-square, ANOVA or Kruskall-Wallis were performed. Results: Three hundred ninety-five patients (mean [SD] age 58 [15] yrs; 51% male, 88% black) were included: 124 (31%) higher dose nitroglycerin, 182 (46%) intravenous nitroglycerin, and 89 (22%) higher dose/intravenous nitroglycerin. While demographics were generally similar between groups, higher dose nitroglycerin patients were more likely to have a history of heart failure (72% versus 53% for intravenous nitroglycerin and 45% for higher dose intravenous nitroglycerin; p<0.001). At baseline, mean systolic blood pressure was significantly greater (p<0.001) in the higher dose/intravenous nitroglycerin group (Figure) while mean [SD] respiratory rate was lower in the intravenous nitroglycerin group (24[7] bpm versus 27 [11] in the higher dose nitroglycerin and 28 [8] higher dose/IV nitroglycerin groups; p<0.001). Most patients (∼75%) received similar mean [SD] intravenous furosemide dosing (64 [32] mg, 69 [53] mg, and 67 [35] mg in the higher dose nitroglycerin, intravenous nitroglycerin and higher dose/intravenous nitroglycerin groups, respectively; p=NS). Mean [SD] total dose of bolus higher dose nitroglycerin was greater in the higher dose/intravenous nitroglycerin group (3.9 [3.7] versus 2.4 [2.6] mg; p=0.001). No difference was found (Table) among the groups in use of bilevel positive airway pressure or endotracheal intubation, ED or ICU length of stay, rate of delayed cardiac injury, inhospital mortality, or out of hospital and alive. The ICU admission rate and total hospital length of stay however, were significantly lower among higher dose nitroglycerin patients and the 30-day heart failure readmission rate was substantial higher for the intravenous nitroglycerin group.Tabled 1 Conclusion: In this single-center, retrospective, unadjusted analysis of primarily African-American patients with acute hypertensive heart failure, nitroglycerin administered by higher dose bolus without concurrent intravenous infusion was associated with a significant decrease in ICU admissions and hospital length of stay. Based on our findings, bolus higher dose nitroglycerin appears to be a viable option for the management of such patients.

De Novo Cluster Attacks after Intravenous Nitroglycerin Therapy (P03.215)

Objective: To describe a unique patient who experienced attacks of cluster headache (CH) after the administration of intravenous nitroglycerin (NTG) for Prinzmetal9s angina. Background NTG is widely utilized in the treatment of angina, and headache is a well-known side effect of this medication in both patients with and without a history of a primary headache disorder, including CH, which likely is from vasodilatory mechanisms. Patients with a prior history of primary headache disorders including CH may experience a delayed attack, characteristic of their typical headache, occurring up to 8 hours after stopping NTG infusion, likely secondary to direct neuronal and inflammatory mechanisms. To our knowledge, no patient has been described to have first onset CH attacks after NTG administration. Design/Methods: Case report from a tertiary medical center. Results: A 43 year old woman who previously only experienced infrequent episodic tension-type headache presented to our hospital with recurrent episodes of severe chest pain over 2 days, and was thought to have an ST-elevation myocardial infraction. Emergent cardiac catheterization revealed severe coronary vasospasm, consistent with Prinzmetal9s angina, and was treated successfully with an intravenous NTG infusion and subsequently verapamil. She subsequently experienced her first ever CH attacks, both within minutes after NTG initiation and 16 hours after its discontinuation. Both attacks were identical and characterized by 60 minutes of excruciating left orbital pain associated with moderate ptosis. Her interictal neurological examination, MRI and MRA of the brain were normal, and she experienced no subsequent attacks. Conclusions: This patient experienced de novo CH attacks from intravenous NTG. The delayed onset of CH attacks strongly suggests a direct neuronal or inflammatory mechanism rather than attacks occurring from intracranial vasodilation. Perhaps a brief cluster period itself was brought on by NTG, which was rapidly suppressed by both withdrawal of the agent and institution of verapamil. Disclosure: Dr. Agopian has nothing to disclose. Dr. Robbins has nothing to disclose.

A Case of Severe Coronary Spasm Associated with 5-Fluorouracil Chemotherapy

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, condition. The case of an 83-year-old man with colon cancer who developed chest pain during 5-FU infusion is presented. The electrocardiogram (ECG) showed pronounced ST elevation in the lateral leads, and the chest pain was resolved after infusion of nitroglycerin. A coronary angiogram (CAG) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery. Coronary artery spasm with fixed stenosis was considered, and a drug-eluting stent was implanted. After 8 hours, the patient complained of recurring chest pain, paralleled by ST elevation on the ECG. The chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine. Repeated CAG showed patency of the previous stent. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-FU cardiotoxicity.

The value of E/Em ratio in the estimation of left ventricular filling pressures: Impact of acute load reduction: A comparative simultaneous echocardiographic and catheterization study

BackgroundThe ratio of the early transmitral flow velocity to the early diastolic tissue velocity (E/Em) has been suggested as a reliable estimate of left ventricular diastolic pressures (LVDP). However, the evidence regarding the ability of E/Em to detect LVDP changes is relatively equivocal. Our aim was to evaluate the validity of the ratio following acute load reduction. Methods and results68 consecutive patients referred for coronary angiography underwent LV catheterization and echocardiography simultaneously. Doppler signals of transmitral flow and spectral TD signals at the level of the mitral annulus were obtained before and directly after intravenous administration of nitroglycerin (NTG). The predictive ability of E/Em to identify elevated LVDP was modest (area under curve=0.71±0.08, p<0.01). The index was more strongly associated with LVDP in patients with reduced ejection fraction (EF)<55% (r=0.68; p<0.01) than in patients with normal EF. Following NTG, E/Em lacked any predictive potential for elevated LVDP whereas changes LVDP could not be reliably tracked using E/Em. ConclusionThe predictive capacity of E/Em for elevated LVDP was weak and declined significantly following acute reduction in LV load. Changes in LVDP were not reliably predicted by E/Em. The current findings derived from a real-world patient population with relatively high filling pressures indicate that E/Em may not be sufficiently robust to be employed as a single non-invasive estimate of LVDP nor for monitoring load reducing medical therapy.

Assessment of Coronary Flow Parameters by Transesophageal Echocardiography in Patients with Isolated Coronary Artery Ectasia: Effect of Intravenous Nitroglycerin

We sought to assess coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. Consecutively, we enrolled 30 patients with ectasia of the left anterior descending (LAD) coronary artery (study group), and 10 subjects with normal coronaries (control group). All patients underwent transesophageal echocardiography to visualize the LAD. Spectral recordings of proximal LAD flow velocities were made and velocity time integrals were calculated. The diameter of the proximal LAD was measured and LAD blood flow was calculated. Nitroglycerin (0.3 mg) was administered intravenously and measurements were repeated 5 minutes later. The mean age of the whole series was 48.6 ± 8 years, 39 (97.5%) being males. A significantly higher baseline systolic, diastolic, and total coronary blood flow was found in the study group as compared to the control group (46.1 ± 34.3 vs. 23.1 ± 8.2, 123.9 ± 73.3 vs. 68.1 ± 21.6, 170.1 ± 97.9 vs. 91.1 ± 26.8 cm(3) /min, respectively, P < 0.05 for all). Within the study group, nitroglycerin administration caused a significant decrease in peak diastolic velocity; systolic, diastolic, and total velocity time integrals; and both diastolic and total coronary blood flow (P < 0.05 for all). Meanwhile, within the control group, nitroglycerin administration caused a significant increase in the total coronary blood flow (P < 0.05). Patients with CAE have higher resting coronary blood flow in comparison with subjects with normal coronaries. Intravenous nitroglycerin administration causes significant reduction of coronary blood flow in ectatic coronary arteries.

Pharmacokinetic interaction between 5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo (4,3-d) pyrimidine-7-one (DA-8159) and nitroglycerin in rats

The pharmacokinetic interaction between 5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo (4,3-d)pyrimidine-7-one (DA-8159), a new erectogenic, and nitroglycerin has been evaluated in rats. Male Sprague-Dawley rats received DA-8159 (30 mg kg(-1)) as a single intravenous or oral dose with the simultaneous single intravenous administration of nitroglycerin (2.5 mg kg(-1)). After simultaneous intravenous administration, the total area under the plasma concentration-time curve from time zero to time infinity (AUC(inf)) of DA-8159 (746 vs 457 microg min mL(-1)) was found to be significantly greater than with DA-8159 alone. Also, after simultaneous intravenous administration total body clearance (CL) (40.2 vs 65.6 mL min(-1) kg(-1)), renal clearance (CL(R)) (1.65 vs 5.11 mL min(-1) kg(-1)), and nonrenal clearance (CL(NR)) (38.3 vs 60.2 mL min(-1) kg(-1)) of DA-8159 were significantly slower compared with DA-8159 alone. The slower CL(NR) of DA-8159 could have been due to the inhibition of the metabolism of DA-8159 by nitroglycerin, since DA-8159 is metabolized via CYP3A1/2 in rats and nitroglycerin inhibits CYP3A1/2 in rats. The slower CL(R) of DA-8159 could have been due to the urine flow rate-dependent CL(R) of DA-8159 in rats. After the simultaneous intravenous administration of nitroglycerin and DA-8159, the AUC(inf) of nitroglycerin was significantly smaller (635 vs 960 microg min mL(-1)), which could have been due to the cardiac output-dependent CL of nitroglycerin. However, after the oral administration of DA-8159, the pharmacokinetic parameters of DA-8159 with and without the intravenous administration of nitroglycerin became comparable. This was not due to the decrease in nitroglycerin's gastrointestinal absorption of DA-8159, but could have been due to changes in nitroglycerin's intestinal firstpass effect of DA-8159. Human studies are required to determine the administration time of DA-8159 when nitroglycerin is concomitantly taken.

Time Course of Hemoglobin Concentrations in the Intensive Care Unit in Nonbleeding Patients With Acute Coronary Syndrome

Critically ill patients commonly show a decrease in hemoglobin concentration during their stay in the intensive care unit. The purpose of the present study was to evaluate whether nonbleeding patients with acute coronary syndrome (ACS) show a similar decrease of hemoglobin, and thereby furnish reference values and analyze possible mechanisms. In this retrospective, descriptive study, the charts of all patients with ACS hospitalized between January 2004 and September 2005 were screened with regard to patient characteristics, time course of hemoglobin, as well as clinical parameters, concomitant drug therapy, and fluid balances. One hundred three nonbleeding patients with ACS were analyzed. They showed an average hemoglobin decrease of 1.27 +/- 1.00 g/dl (p <0.001). The decrease in hemoglobin level was observed during the first 12 to 24 hours; thereafter the hemoglobin concentration remained stable. We found a correlation among decrease of hemoglobin, parameters of stress, such as hypertension (p = 0.019), tachycardia (p = 0.004), pain (p = 0.043), and white blood cells (p = 0.021), as well as the intravenous administration of nitroglycerin (p = 0.004). In conclusion, during the first 24 hours in the intensive care unit the hemoglobin concentration of nonbleeding patients with ACS regularly decreases at 1.27 +/- 1.00 g/dl. Any further decrease in hemoglobin level beyond these values should entail early active search of the bleeding source. We hypothesize that this decrease is due to normalization of the previous stress-induced hemoconcentration and "internal hemodilution" by nitroglycerin.

Effectiveness of intravenous administration of nicorandil in a patient with variant angina refractory to continuous intravenous nitroglycerin

Variant angina usually responds to conventional treatment with nitrates and calcium antagonists. However, severe variant angina refractory to intensive anti-anginal treatment can be catastrophic because prolonged occlusion of a major coronary artery can result in myocardial infarction, severe cardiac arrhythmia, and sudden death. We report a patient with active variant angina which was refractory to conventional treatment including sublingual nitroglycerin and intravenous nitroglycerin administration. Only intravenous administration of nicorandil was consistently effective in eliminating chest pain of the patient.

Pressure tracings in obstructive Tako‐Tsubo cardiomyopathy

A 70-year-old female experienced severe anxiety due to an incident with a stranger when she was home alone at night. Immediately after the event, she had an oppressive chest sensation; 16 h later she was admitted to hospital. Left ventriculography showed akinesia of the mid-to-distal portion and hyperkinesia of the basal portion of the left ventricular chamber. However, coronary angiography showed no significant coronary artery disease. We diagnosed her as having Tako-Tsubo cardiomyopathy. Subsequently, left ventricular and central aortic pressures were recorded simultaneously. Initial recording showed a peak systolic gradient of 60 mm Hg. On the first sinus beat after a premature ventricular contraction, the peak systolic gradient increased to 130 mm Hg, and the pulse pressure decreased. Shortly after intravenous administration of nitroglycerin (0.5 mg), central aortic pressure decreased and the peak systolic gradient increased to 100 mm Hg. On the first sinus beat after a premature ventricular contraction, the peak systolic gradient increased to 160 mm Hg, and the pulse pressure decreased. Five minutes after intravenous nitroglycerin, the peak systolic gradient returned to 70 mm Hg. Follow-up transthoracic echocardiography 13 days later showed normal left ventricular wall motion with no pressure gradient through the left ventricular outflow tract.

Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning

Previous studies have shown that the cardioprotective effect of ischemic preconditioning (IPC) can be mimicked pharmacologically with clinically relevant agents, including nitric oxide (NO) donors. However, whether pharmacological preconditioning shares the same molecular mechanism with IPC is not fully elucidated. The present study aimed to determine the activation of mitogen-activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared to IPC and to correlate this with the conferred cardioprotection in anesthetized rabbits. Sixty minutes of intravenous administration of nitroglycerin was capable of inducing both early and late phase preconditioning in anesthetized rabbits, as it was expressed by the reduction of infarct size. Despite the cardioprotective effect conferred by both ischemic and nitroglycerin-induced preconditioning, there was a differential phosphorylation of MAPKs between the studied groups. p38 MAPK was activated early in ischemia in both ischemic and the early nitroglycerin-induced preconditioning while JNKs were markedly increased only after IPC. Furthermore, in these groups, ERK1/2 were activated during reperfusion. A different profile was observed in the late preconditioning induced by nitroglycerin with increased p38 MAPK and ERK1/2 phosphorylation during late ischemia. No activation of JNKs was observed at any time point in this group. It seems that activation of individual MAPK subfamilies depends on the nature of preconditioning stimulus.

Intravenous nitroglycerin does not preserve gastric microcirculation during gastric tube reconstruction: a randomized controlled trial

IntroductionComplications of oesophagectomy and gastric tube reconstruction include leakage and stenosis, which may be due to compromised microvascular blood flow (MBF) in gastric tissue. We recently demonstrated that decreased MBF could be improved perioperatively by topical administration of nitroglycerin. The aim of the present study was to investigate whether nitroglycerin, administered intravenously during gastric tube reconstruction, could preserve tissue blood flow and oxygenation in the gastric fundus, and reduce the incidence of postoperative leakage.MethodsIn this single-centre, prospective, double-blinded study, we randomized 32 patients scheduled for oesophagectomy into two groups. The intervention group received intravenous nitroglycerin during gastric tube reconstruction, and the control group received normal saline. Baseline values for MBF, microvascular haemoglobin oxygen saturation and microvascular haemoglobin concentration were determined at the gastric fundus before and after gastric tube construction and after pulling up the gastric tube to the neck.ResultsMBF and microvascular haemoglobin oxygen saturation decreased similarly in both groups during gastric tube reconstruction and were comparable. The oesophageal anastomosis was controlled by contrast radiography before discharge from the hospital; leakage was observed in two patients (13%) in the nitroglycerin group and five patients (31 %) in the control group (not significant).ConclusionUnder stable systemic haemodynamic conditions, continuous intravenous administration of nitroglycerin could not prevent deterioration in gastric microvascular perfusion and microvascular haemoglobin saturation during gastric tube reconstruction. (Trial registration number NCT 00335010.)

Impact of preoperative intravenous nitroglycerin on in-hospital outcomes after coronary artery bypass grafting for unstable angina

Abstract Background Intravenous nitroglycerin (NTG) is an effective therapy for unstable angina (UA), but it may induce endothelial dysfunction and impair vascular nitric oxide signaling. We sought to determine whether preoperative intravenous NTG administration alters in-hospital outcomes in patients undergoing coronary artery bypass grafting (CABG) for UA. Methods and results All in-hospital patients with Canadian Cardiovascular Society class IV angina who had isolated CABG between March 1995 and July 2002 at two Canadian centers were identified (n = 3976). Of these, 2506 were not receiving intravenous NTG and 1470 were receiving intravenous NTG at the time of CABG. Outcomes assessed were in-hospital mortality (IHM), intraoperative or postoperative aortic balloon pump use, perioperative myocardial infarction, prolonged (≥24 hours) ventilation (p-vent), and a composite outcome, defined as any one or more of the above. Unadjusted IHM (5.9% vs 4.2%, P = .02), p-vent (22.2% vs 10.5%, P = .0001), and composite outcome (26.5% vs 15.2%, P = .0001) were higher in patients receiving intravenous NTG. Logistic regression showed that preoperative intravenous NTG was not an independent predictor of composite outcome (OR, 1.1; P = .49) or IHM (OR, 0.94; P = .69). Propensity score analysis was used to match two subgroups of patients (group 1, intravenous NTG, n=1176; group 2, no intravenous NTG, n=1176) on multiple factors. After adjustment with the propensity score, preoperative intravenous NTG use had no significant effect on any of the outcomes assessed. Conclusions Despite its potential to induce endothelial dysfunction and impair vascular nitric oxide signaling, preoperative intravenous NTG administration is not associated with altered in-hospital outcomes after CABG for UA.

Resolution of ST-segment elevation following intravenous administration of nitroglycerin and verapamil

cantly higher rates of peri-interventional bleeding among patients with impaired renal function. Multivariate analysis of the registry data showed an independent association of renal insufficiency with bleeding complications under abciximab (odds ratio 5.1; 95% confidence interval 1.9 to 13.8). Success rates after PCI under abciximab were comparable in patients with normal and impaired renal function. These data suggest that the effects of abciximab are not entirely independent of renal function. Further investigation of this subject is neces

Espasmo coronario tras infusión de propranolol durante un ecocardiograma de estrés con dobutamina

Dobutamine stress echocardiography, a highly useful and safe challenge test for myocardial ischemia, is being used increasingly. We report the case of a 37-year-old man with rest angina, repolarization abnormalities in precordial leads and normal coronary arteries who was referred for dobutamine-atropine stress echocardiography, which was negative for ischemia. However, after testing, upon injection of propranolol, the patient suffered chest pain associated with ST elevation and severe regional systolic abnormalities. After intravenous nitroglycerin administration, chest pain and electrocardiographic abnormalities disappeared quickly, and systolic motion became normal. This complication was interpreted as a coronary spasm. We discuss the causes for the spasm and the role that might have been played by the drugs employed.

Impact of intravenous nitroglycerin on pulsed Doppler indexes of left ventricular filling in acute anterior myocardial infarction

Background Restrictive transmitral Doppler flow patterns are associated with heart failure in acute myocardial infarction (AMI). Methods and Results The objective of this study was to evaluate the effect of intravenous nitroglycerin on the transmitral pulsed Doppler patterns in patients with anterior AMI. Twenty-four patients with anterior AMI were randomly assigned to receive incremental intravenous nitroglycerin or placebo over a 16-minute period with change to the other arm after a washout period. Left ventricular filling was assessed with transmitral pulsed Doppler echocardiography. According to the baseline E/A ratio, patients were divided into a restrictive group ( n = 17, E/A ratio ≥1.4) and a nonrestrictive group ( n = 7, E/A <1.4). In the restrictive group after administration of nitroglycerin the E/A ratio decreased (1.9 ± 0.7 to 1.1 ± 0.2, P < .001), E-wave peak velocity decreased (71 ± 10 to 60 ± 9 cm/s, P < .01), and A-wave peak velocity increased (39 ± 9 to 58 ± 8 cm/s, P < .01). In the nonrestrictive group there were no significant changes after nitroglycerin infusion in the E/A ratio (1.1 ± 0.2 to 0.8 ± 0.1, not significant), peak E-wave velocity (55 ± 4 to 47 ± 6 cm/s), and peak A-wave velocity (49 ± 8 to 52 ± 8 cm/s). Deceleration time increased significantly in both groups after administration of nitroglycerin. Placebo did not result in significant changes in hemodynamic or Doppler parameters in either group. Conclusions Intravenous nitroglycerin administration was associated with reversal of restrictive left ventricular diastolic filling pattern on pulsed wave Doppler in patients with anterior AMI. (Am Heart J 1998;136:812-7.)