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PubMed1995

Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers.

Nicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18-32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscular femoral (FA) and brachial (BA) arteries were investigated. The effects on systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and venous hemodynamics were also assessed. In addition, the subacute effects after 8 days of treatment with N (2 x 20 mg/day) and ISDN (3 x 20 mg/day) on these parameters were evaluated. After a 20 mg single oral dose, blood pressure decreased significantly more with ISDN (SBP: 6%; DBP: 14%) than with N (SBP: 2%; DBP: 6%), but after 8 days this decrease in blood pressure was not statistically different between ISDN and N. The diameter of CCA increased more with ISDN (11%) than N (5%) acutely as well as subacutely (ISDN: 12%; N: 9%). Heart rate increased only with ISDN (7% acutely, 3% subacutely). No differences between ISDN and nicorandil were found for acute and subacute effects on SVRI, venous hemodynamics, diameter of muscular arteries (FA, BA), and the distensibility and compliance of elastic (CCA) and muscular (FA, BA) arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1982

Comparative study of the haemodynamic effects of oral molsidomine and isosorbide dinitrate in man.

The haemodynamic effects of oral molsidomine 4 mg and sustained-release isosorbide dinitrate (ISDN) 40 mg have been compared in 10 patients recovering from acute myocardial infarction. After both drugs pulmonary arterial, pulmonary capillary wedge and systemic arterial blood pressure were reduced to about the same extent. The maximum effect was reached 1.5 to 2 h after ingestion of both drugs, but the effect of molsidomine declined during the following 2 h and control values were almost reached after 4 h. After ISDN there was no rebound during the observation period of 6 h. Unlike molsidomine, ISDN reduced total peripheral resistance, so cardiac output and stroke volume index remained constant despite the reduction in cardiac preload. It is concluded that sustained release ISDN 40 mg and molsidomine 4 mg are about equieffective doses in terms of reduction of cardiac preload, but that the effect of molsidomine is of shorter duration. Since molsidomine alone causes venous pooling, cardiac output and stroke volume index are reduced, which may be an untoward side effect in patients with severe heart failure.

Cardiac Output↗
PubMed1990

Lack of tolerance after chronic administration of controlled-release isosorbide-5-mononitrate. Interaction of nitrate and gallopamil.

The effect of a controlled-release formulation of isosorbide-5-mononitrate (IS-5-MN) was studied in patients with coronary heart disease (CHD), with the aim of comparing the acute effect with that after chronic administration on parameters of ischemia. To determine whether any tolerance developed, several aspects of ischemia were observed: ECG signs, clinical parameters, and left ventricular function. Fifteen patients with angiographically proven CHD were examined with 12-lead exercise ECG before, 2 h and 4 h after the first dose and after 10 days of therapy with 60 mg IS-5-MN (Coleb-Duriles) once daily. After 7 days, three radionuclide ventriculographies were performed: control, 2 h after nitrate and 2 h after 75 mg gallopamil. Plasma concentrations of IS-5-MN were measured before every exercise test. The results showed a reduction of total ST-segment depression from 0.59 mV to 0.29 mV after 2 h (NS) and 4 h (P less than 0.05) on the 1st day and from 0.48 mV to 0.32 mV (P less than 0.05) and 0.31 mV (NS) after 10 days. The severity of angina pectoris was diminished by about 50%. The effect on exercise duration and time to ST-segment depression by more than 0.1 mV remained unchanged after 10 days, whereas the effect on blood pressure, heart rate and time to onset of angina was attenuated. The mean decrease in ejection fraction (EF) from rest to exercise was reduced from--5.9% to -1.9% (P less than 0.05) after nitrate, while an increase of +1.4% was seen after gallopamil (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate.

Healthy male volunteers received three different dose regimens of a controlled-release form of isosorbide-5-mononitrate (IS-5-MN; 60 mg per tablet). Dose regimen I consisted of a single daily dose of 60 mg given for 5 days. Dose regimen II was started with a dose of 60 mg, followed by 30 mg 12 h later and thereafter every 8 h. The last dose, on the 5th day was again 60 mg. In dose regimen III 60 mg followed by 30 mg 6 h later were administered every day for 5 days. The peripheral arterial and venous effects of IS-5-MN during the first and last dosing interval were followed by changes in the finger pulse curve, standing systolic blood pressure, heart rate, and venous distensibility. Plasma concentrations of IS-5-MN were measured frequently following the first and the last dose. Following dose regimen I all hemodynamic effects produced by the first dose were maintained during the study. The maximal plasma concentrations were about 400 ng/ml and the trough value, lower than 100 ng/ml. Following dose regimen II the hemodynamic effects of IS-5-MN and sublingual glyceroltrinitrate were completely abolished on the 5th day. Trough plasma concentrations were approximately 300 ng/ml during the entire study period. Following dose regimen III pronounced hemodynamic effects were seen on the 1st day. However, a significant attenuation of the hemodynamic effects was measured on the 5th day, when trough plasma concentrations were between 100 and 230 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Anti-ischemic and antianginal effects of 60 mg isosorbide-5-mononitrate in patients treated chronically after myocardial infarction.

25 patients with stable angina pectoris after acute myocardial infarction were given single and maintenance doses of isosorbide-5-mononitrate (IS-5-MN) in a controlled-release formulation. For evaluation of the efficacy of this treatment, a score based on exercise tests and patient's complaints including additional antianginal medication were used 4 weeks after the acute event. For assessment of anti-ischemic effect non-invasive parameters including heart rate, arterial blood pressure, changes in ST segments, frequency of premature ventricular beats and systolic time intervals were used before medication, 5 h after the initial dose and 7 days after maintenance therapy. The therapeutic concept of interval treatment was found to be effective. Nitrate tolerance did not develop. Measurements of plasma levels under steady-state conditions revealed minimum values of 100 ng/ml and maximum levels of 460 ng/ml which is in between the threshold for anti-ischemic effect and development of nitrate tolerance, respectively.

Adult↗
PubMed1985

[Anti-angina effectiveness of isosorbide dinitrate in an acute trial and following continuous 4-week therapy with 40 mg 6 times a day].

Ten patients with angiographically proven coronary heart disease, stable exercise-induced angina pectoris, and reproducible ST-segment depression were treated with isosorbide dinitrate (ISDN) tablets in daily doses of 240 mg (6 X 40 mg) and placebo (PL) for 28 days each on the basis of a randomized double-blind protocol with intraindividual cross-over. ISDN treatment resulted in a sustained reduction of anginal attacks with a weekly mean rate ranging from 1.4 (3rd week) to 3.9 (4th week) as compared to 10.2 (2nd week) to 11.7 (4th week) during placebo treatment (P less than 0.001). Ischemic response during stress testing (sum of ST-segment depressions) was significantly improved during ISDN treatment as compared to placebo. Day 1: 56% (P less than 0.01); day 7: 30% (P less than 0.01); day 28: 49% (P less than 0.001). Heart rate and arterial blood pressure in the upright position were different between ISDN and placebo on day 1 and day 7 of the treatment phases (P less than 0.02), but not on day 28. Nitrate responsiveness with regard to blood pressure and heart rate was restored after a drug-free interval of 2 days. The plasma concentrations for ISDN and the mononitrate metabolites exhibited a constant ratio during the treatment period. Thus, therapy with 6 X 40 mg ISDN per day resulted in a sustained reduction of anginal attacks and preserved improvement of ischemic ST-segment depression during exercise in upright position.

Adult↗
PubMedDate not supplied

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog.

Platelet activation and aggregation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Molsidomine (M), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) have been found to inhibit platelet aggregation in vitro. In the present study, the activity of these compounds was investigated in a model of coronary artery thrombosis in vivo. Dogs were anesthetized, thoracotomized, and their heart was exposed. An electrode was inserted into the left circumflex coronary artery and set to rest on the intima. Electrical stimulation (9 V, 150 microA) lasted for 6 h. Compounds (each in 2 dose levels) were given as an i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (saline-treated) animals underwent thrombotic occlusion of the coronary artery as assessed by flow measurement. On the other hand, 2/8 dogs treated with the lower M dose and 4/8 dogs treated with the higher M dose did not have a coronary occlusion. Neither ISDN nor NTG, at both doses, prevented the coronary occlusion. In control animals thrombus wet weight was 74.43 +/- 11.25 mg. M reduced the thrombus weight in a dose-related manner, while ISDN (marginally) and NTG (significantly at the higher dose) increased this parameter. Following the coronary thrombosis, all control animals developed myocardial infarcts as assessed by the tetrazolium technique. Similarly all animals treated with ISDN and with NTG (at both doses) showed infarcts. However, 3/8 M-dogs did not have a myocardial infarction in the lower as well as in the higher dose groups. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M but not ISDN or NTG showed in this in-vivo study antithrombotic and consequently antiischemic activity.

Animals↗
PubMed1996

The value of Tc-99m MIBI SPECT during isosorbide dinitrate infusion in assessment of viable myocardium in patients with myocardial infarction.

Tc-99m MIBI myocardial SPECT has shown promise for evaluation of coronary artery disease. But its role in predicting myocardial viability is still under investigation. The purpose of this study was to evaluate the value of Tc-99m MIBI myocardial SPECT during isosorbide dinitrate (ISDN) infusion in the assessment of myocardial viability. Thirty-seven patients with previous myocardial infarction (the infarct age ranged from < or = 30 days to 900 days) were studied, of them 13 patients had Tc-99m MIBI studies before and after coronary artery bypass grafting (CABG). The results showed that out of 134 segments with hypoperfusion at resting SPECT, 56 segments (41.8%) had an increase in Tc-99m MIBI uptake during ISDN infusion. Among them, 17 segments (30.4%) were normalized, 6 segments (10.7%) were significantly improved and 33 segments (58.9%) were improved. The degree of improvement in perfusion was related to the age of the myocardial infarction. In 13 patients with CABG, of 31 segments with improvement in perfusion post CABG, 25 segments (80.6%) showed perfusion improvement during ISDN infusion, and of 28 segments with improved wall motion post CABG, 23 segments (82.1%) showed improvement in perfusion during ISDN infusion. Tc-99m MIBI SPECT during ISDN infusion may therefore be a useful approach for assessing myocardial viability.

Adult↗
PubMed1997

Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man.

Arginine has well-known stimulatory effects on GH, PRL and insulin secretion in man but the mechanisms underlying these effects are still unclear. More recently, it has been demonstrated that arginine is the precursor of nitric oxide (NO) which mediates its vasodilatatory effect. Thus, it has been hypothesized that NO could also mediate the hormonal effects of arginine. To clarify this point, in seven normal young volunteers (7 normal male subjects, age 26-35 yr) we compared the effects of arginine hydrochloride (ARG, 0.5 g/kg iv over 30 min) on GH, PRL, insulin and glucose levels as well as on blood pressure, with those of isosorbide dinitrate (ISDN, 5 mg po) and molsidomine (MOLS, 4 mg po), two NO donors which possess well-known vasodilatatory effects. ARG infusion elicited a clear-cut GH increase (peak vs baseline 17.6 +/- 4.7 vs 2.7 +/- 0.8 (g/L, p < 0.01), PRL (20.6 +/- 2.8 vs 6.9 +/- 0.5 (g/L, p < 0.01) and insulin levels (31.4 +/- 5.7 vs 4.5 +/- 2.1 (U/L, p < 0.01) while induced a biphasic variation of plasma glucose levels with early increase (p < 0.01), followed by late decrease below basal values (p < 0.01). On the other hand, blood pressure was decreased by ARG (nadir vs baseline; systolic: 103 +/- 6 vs 112 +/- 3, p < 0.02 and diastolic 61 +/- 4 vs 72 +/- 2 mmHg, p < 0.02, respectively). ISDN and MOLS did not modify basal GH, PRL and insulin as well as glucose levels while induced a clear reduction in blood pressure (ISDN: nadir vs baseline; systolic: 94 +/- 4 vs 112 +/- 2, p < 0.02; diastolic 69 +/- 3 vs 80 +/- 2, p < 0.02; MOLS: systolic: 94 +/- 3 vs 113 +/- 2 p < 0.02; diastolic 63 +/- 4 vs 72 +/- 2, p < 0.02). The lowering effect of both ISDN and MOLS on both systolic and diastolic blood pressure levels was higher than that induced by ARG. The effect of the latter was, in turn, significantly different from that of placebo on diastolic levels only. In conclusion, our present date are against the hypothesis that NO mediates the stimulatory effects of arginine on GH, PRL and insulin secretion. On the other hand, our findings agree with the hypothesis that ARG has NO-mediated vasodilatatory effect able to decrease blood pressure in man.

Adult↗
PubMed2001

Local effect of transdermal isosorbide dinitrate ointment on hand vein diameter.

OBJECTIVE: To assess the effect of topically applied isosorbide dinitrate (ISDN) ointment on superficial hand veins preconstricted with phenylephrine. METHODS: Using the hand vein compliance technique, venous diameter changes were measured in a double-blind, randomised, placebo-controlled cross-over trial in 12 healthy volunteers. During preconstriction with phenylephrine, placebo or ISDN ointment was administered to assess the dilator effect of transdermal ISDN. Finally a single i.v. dose of nitroglycerine was administered into the hand vein to assess the maximal venous response to organic nitrovasodilators. RESULTS: ISDN ointment (equivalent to 13.4 +/- 3.61 mg ISDN) caused a significant dilator effect of 39.1 +/- 21.7% (mean +/- SEM, P=0.02) which reached its maximum after 42.5 +/- 16.6 min. Maximum ISDN effects were inversely correlated with venous baseline diameter (r2=0.38, P=0.03) and independent of the amount of ointment applied or the extent of preconstriction (P > 0.3). CONCLUSION: Similar to nitroglycerine, topical ISDN may relax superficial hand veins within 60 min after application, suggesting that it might ease venepuncture particularly of small vessels. The large variability of the effect and the time to reach the effect, however, restrict its practical usefulness.

Administration, Cutaneous↗
PubMed2003

Sublingual isosorbide dinitrate-stimulated tilt test for diagnosis of vasovagal syncope in children and adolescents.

Vasovagal syncope is the most likely cause of syncope in the young. Head-up tilt-table test (HUT) provides the ability to provoke vasovagal syncope under controlled laboratory settings. In adult populations, pharmacologic stimulation with intravenous/sublingual isosorbide dinitrate (ISDN) has been shown to be an alternative to isoproterenol for increasing the diagnostic yield of HUT. In this study, 40 patients aged 9-18 years with unexplained syncope and 12 healthy age-matched children were evaluated by HUT to 70 degrees for 45 minutes. If tilting alone did not induce symptoms (syncope and presyncope), 0.1 mg/kg ISDN was given while the patient lay supine. After 5 min, the table was tilted to 70 degrees for 15 min or until the symptoms occurred. The control group consisted of 12 healthy age-matched children studied in a similar manner. Six patients (15%) had a positive basal tilt test. Twenty-five patients (62.5%) lost consciousness following ISDN administration. In the control group, nobody had a syncopal episode during the basal tilt test. However, ISDN administration resulted in 1 positive response (8.3%). The sensitivity of the test was 77.5% and its specificity was 91.6%. It is concluded that sublingual nitroglycerin HUT is suitable for routine clinical practice in children and adolescents with unexplained syncope.

Administration, Sublingual↗
PubMed2006

Trapidil is as effective as isosorbide-dinitrate for treating stable angina pectoris: a multinational, multicenter, double-blind, randomized study.

OBJECTIVE: Nitrates have long been used in the treatment of stable angina pectoris. We set out to show that trapidil, a triazolo-pyrimidine with a mode of action different from that of nitrates, is not inferior to isosorbide-dinitrate (ISDN) in the treatment of this clinical syndrome. PATIENTS AND METHODS: We studied the efficacy of 200 mg trapidil (t.i.d.) vs. ISDN (20 mg b.i.d.) in patients with chronic stable angina treated for 12 weeks. The therapeutic effect was measured in terms of responder rate as change in total exercise time (TET) by at least 60 seconds using the bicycle ergometer test. RESULTS: A total of 648 patients were included in the study. Responder rates in the Per- Protocol (PP) population (n = 529) were 50.4% (n = 133) in the trapidil group and 52.5% (n = 139) in the ISDN group (p = 0.233). As the lower non-inferiority limit (-15%) was clearly excluded from the 95% CI (pp: -10.6%, +6.4%; ITT -9.7%, 5.7%), non-inferiority of trapidil compared to ISDN can be concluded. Trapidil 200 mg t.i.d. combined with short-acting NTG prn as rescue medication over 12 weeks in subjects with chronic stable angina pectoris proved to have similar effects on TET and on other clinical endpoints as ISDN 20 mg b.i.d. The secondary efficacy analyses did not reveal any clinically relevant differences between treatment groups, and were not in conflict with the non-inferiority claim. Patients in the ISDN group had significantly more headache (34.1%; n = 110) compared to those taking trapidil (19.3%, n = 62; p <0.0001). CONCLUSIONS: Overall results of this study show that both drugs are equally effective and safe for the short-term treatment of patients with chronic stable angina pectoris and that trapidil can be considered as therapeutically equivalent to ISDN.

Adult↗
PubMed2001

[Anti-ischemic efficacy of sustained-release isosorbide-5-mononitrate: echocardiography during mental and physical stress].

This double-blind, placebo-controlled study investigated the anti-ischemic efficacy of sustained-release isosorbide-5-mononitrate (IS-5-MN) 100 mg/day on the basis of stress echocardiography and stress ECG in patients subjected to physical (bicycle ergometry) and mental stress (mental stress test). Forty male patients with a stress-induced ST segment depression of > 0.1 mV during bicycle ergometry who received beta blocker background therapy were randomized into the 14-day treatment phase (IS-5-MN: 20 patients, placebo: 20 patients). After 2 weeks of treatment, a significant prolongation of the time to 0.1 mV ST segment depression and of the time to stress-induced anginal attacks could be demonstrated for IS-5-MN in the stress echocardiography. A significantly greater reduction in the wall motion score determined via stress echocardiography was found in IS-5-MN-treated vs. placebo-treated patients relative to baseline. There were only 4 patients who developed ST segment depression during mental stress; however, the echocardiography demonstrated a significantly greater reduction of the wall motion score after 2 weeks of treatment vs. baseline in the IS-5-MN vs. the placebo group. The efficacy of sustained-release IS-5-MN 100 mg/day was proved in this study both by stress echocardiography, and stress electrocardiography in situations of physical and mental stress. It was found that echocardiography is more sensitive for detecting ischemic reactions induced by mental stress than ECG.

Adult↗
PubMed1982

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm.

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.

Adult↗
PubMed1985

History of the synthesis and pharmacology of isosorbide dinitrate.

A major research program in the University of Maryland School of Medicine, Department of Pharmacology, in the 1930s was the preparation of a large number of sugar alcohols and their anhydrides as substitute carbohydrates for diabetic diets. As an outgrowth of this work, many of these polyols were converted to their nitrate esters and investigated for their vasodilating properties. The organic nitrates that were synthesized were examined for their potency, duration of action, and possible therapeutic use. It was demonstrated that, contrary to prior belief, the depressor and vasodilating action was exhibited by their own molecular structure and not through hydrolysis and reduction to nitrite. The search for the finer mechanism(s) of action on the vascular musculature showed that these nitrated polyols and their anhydrides inhibited arterial adenosine triphosphatase, although this enzyme inhibition did not correlate with pharmacologic activity. Today the mechanism of action of these drugs is not clearly understood at the cellular level. The 1,4:3,6-dianhydrosorbitol 2,5-dinitrate (isosorbide dinitrate) was synthesized, studied, and reported in 1940. It appeared to be a useful drug because blood levels of the unhydrolyzed ester were found to persist for long periods of time. Subsequent clinical studies in the 1960s demonstrated its prophylactic value in angina pectoris and its prolonged action as a therapeutic asset. In 1967 the mononitrate was shown to be formed in vivo when the dinitrate was administered orally and has been studied as the possible pharmacodynamically active moiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1985

Arteriographic demonstration of the release of coronary artery spasm by isosorbide dinitrate: a twenty-five-year retrospective.

It has been 25 years since my colleagues and I were first approached to apply the then newly emerging technique of coronary arteriography to the study of the effects of the new vasodilator isosorbide dinitrate (ISDN) on coronary arteries in vivo. Through a combination of careful patient assessment and serendipity, we were able to visualize the prompt release of coronary artery spasm by ISDN. Ensuing years have seen dramatic advances both in angiographic techniques and in the knowledge of ISDN efficacy. This review will briefly summarize the early work with ISDN and detail how the improvements in cineangiography have fostered better understanding of the actions of ISDN.

Cineangiography↗
PubMed1985

Studies on the mode of action of isosorbide dinitrate: a physiologic and biochemical approach.

The action of isosorbide dinitrate (ISDN) and diltiazem on coronary artery diameter, vascular resistance, and coronary blood flow was determined in instrumented postoperative conscious dogs. Low doses of ISDN were found to increase the diameter of large arteries without affecting coronary blood flow. Higher doses of ISDN produced an increase in both coronary diameter and blood flow. Diltiazem, on the other hand, increased coronary artery diameter and blood flow at all doses tested. Coronary vascular resistance was more sensitive to diltiazem than to ISDN. In isolated canine cardiac Purkinje strands, ISDN produced a concentration-dependent decrease in force development and action-potential duration measured at 50% of repolarization (APD50). ISDN did not significantly affect action potentials recorded in Purkinje strands depolarized by potassium (22 mmol) and treated with isoproterenol (10(-6)M). Diltiazem also decreased Purkinje strand force development and APD50 in a concentration-dependent manner. Diltiazem, however, was several orders of magnitude more potent than ISDN and completely abolished action-potential genesis in potassium-depolarized, isoproterenol-restored Purkinje strands. Both diltiazem and ISDN were found to relax porcine coronary artery strips contracted by KCl or histamine. Studies on 45Ca flux, in isolated coronary artery rings, indicate that ISDN inhibited both histamine-induced Ca++ influx and efflux from intracellular sources. The inhibition of Ca++ efflux and intracellular Ca++-dependent contraction occurred over a similar ISDN concentration range. ISDN also relaxed bovine coronary artery strips contracted with KCl. No change in cyclic adenosine monophosphate levels occurred during ISDN-induced relaxation of bovine coronary arterial strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗