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Biomedical subjects

D J Coltart

Publications and source records attributed to D J Coltart.

At least 55 records · Page 3Linked to original sources
PubMed1984

Acute effects of ketanserin on left ventricular function, metabolism and coronary blood flow.

An acute intravenous bolus of 10 mg ketanserin (a specific 5-HT antagonist) caused an abrupt fall in left ventricular systolic pressure of 17 +/- 9.2 mm Hg (P less than 0.025) in ten patients undergoing cardiac catheterisation for chest pains. A fall in pulmonary artery diastolic pressure of 2.1 +/- 0.74 mm Hg (P less than 0.02) was also observed. No changes in resting heart rate occurred and the response to pacing was largely unmodified by ketanserin, except for a reduction in pulmonary vascular resistance (3.70 +/- 1.27 units to 2.97 +/- 1.44 units, P less than 0.05), at the fastest rate (136 +/- 3 beats/min). At the highest pacing rate coronary sinus blood flow fell (83 +/- 12 ml 100 g-1 min-1 to 68 +/- 8 ml 100 g-1 min-1, P less than 0.05), as did myocardial oxygen consumption (18 +/- 2 ml-1 min to 14 +/- 1 ml min-1, P less than 0.05) after the drug. No changes in the parameters of left ventricular contractile function could be attributed to ketanserin, save for a modest increase in the ejection fraction (48 +/- 6% to 57 +/- 6%, P less than 0.05) in seven patients. There were no alterations in myocardial metabolism of lactate, pyruvate, hydroxybutyrate, glycerol nor free fatty acids after ketanserin. The findings are consistent with a peripheral site of action of this drug and its blood pressure lowering effect in the subjects suggest a non-specific hypotensive action rather than an anti-hypertensive effect.

Adult↗
PubMed1984

Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy.

The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.

Adult↗
PubMed1984

Ischemia and reperfusion-induced arrhythmias in the rat. Effects of xanthine oxidase inhibition with allopurinol.

We have investigated the possibility that xanthine oxidase-linked free radical production has a role in the genesis of arrhythmias during ischemia and reperfusion. In this study, rats were treated with allopurinol (20 mg/kg, orally, 24 hours before study, plus 20 mg/kg, iv, 15 minutes prior to study). Using an anesthetized open-chest preparation with either coronary artery occlusion for 30 minutes, or 5 minutes followed by 10 minutes reperfusion, we monitored and compared the rhythm disturbances in experimental vs. placebo-treated rats (n = 18 in each group). Allopurinol treatment reduced the incidence of ventricular tachycardia during ischemia from 88% to 50% (P less than 0.05) and the number of premature ventricular complexes from 471 +/- 120 to 116 +/- 46 (P less than 0.02), but the treatment had no effect upon the incidence or duration of ventricular fibrillation or upon mortality. In contrast, far more dramatic protection was observed during reperfusion after 5 minutes of ischemia. Allopurinol treatment reduced the incidence of ventricular fibrillation from 67% to 11% (P less than 0.01), reduced the mean duration of fibrillation from 230 +/- 70 to 14 +/- 1 seconds (P less than 0.05), and reduced mortality by half (10/18 to 4/18), although this did not reach a level of statistical significance. In addition, the mean duration of tachycardia was reduced from 83 +/- 26 to 38 +/- 8 seconds (P less than 0.05). Allopurinol pretreatment thus affords some protection against ischemia-induced arrhythmias, but a higher degree of protection against reperfusion-induced arrhythmias. Allopurinol inhibits xanthine oxidase activity, and, in turn, this inhibits superoxide radical production.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1983

The relationship between glucose utilization during ischemia and ventricular fibrillation during early reperfusion. Evidence for two populations of guinea pig hearts.

Guinea pig hearts perfused in the presence of 9 mM glucose were subjected to 30 min of ischemia (coronary flow reduced to 6%) and were then reperfused. During reperfusion, 18 of the 34 hearts studied (first subgroup) exhibited irreversible ventricular fibrillation. The remaining 16 hearts (second subgroup) exhibited serious rhythm disturbances but did not fibrillate. Attempts to identify critical factors that might precipitate fibrillation led to an observation that hearts that fibrillated during reperfusion were characterized by low rates of glucose utilization (0.6 +/- 0.8 mumol/min per g dry wt. and low lactate plus pyruvate production (2.5 +/- 0.32 mumol/min per g dry wt.) during ischemia. In addition, these hearts had a low calculated cytoplasmic ATP-to-ADP ratio (10.0) and low residential glycogen levels (55 +/- 7.0 mumol glucose equivalents/g dry wt.) at the end of the ischemic period. In contrast, in hearts that did not fibrillate (group 2), glucose utilization (2.5 +/- 0.12 mumol/min per g dry wt.) was higher, lactate plus pyruvate production was higher (7.4 +/- 0.03 mumol/min per g dry wt.), cytoplasmic ATP-to-ADP ratio was higher (36.0), and residual glycogen levels were higher (163 +/- 23 mumol glucose equivalents/g dry wt.). Thus, two distinct populations of guinea pig hearts were apparent, and comparison between the two groups indicated an association among glucose utilization, cytoplasmic energy status, and myocardial electrical stability.

Adenosine Diphosphate↗
PubMed1983

The effect of beta blockade and partial agonist activity during myocardial ischemia.

In this study, we have investigated the importance of partial agonist activity during myocardial ischemia by comparing the effects of equiblocking doses of oxprenolol, which possesses partial agonist activity, to propranolol which does not. In the isolated, globally ischemic (low-flow) rat heart, when propranolol or oxprenolol was added alone during the ischemic period, only propranolol reduced enzyme leakage relative to control. However, when the hearts were perfused (10 min) prior to ischemia with these drugs, both beta blockers caused a significant reduction in enzyme leakage. Under conditions of enhanced sympathetic drive (in the presence of 0.01 microM isoproterenol), both beta blockers reduced enzyme leakage to differing extents. In hearts with low sympathetic drive (reserpine pretreatment), enzyme leakage was unaffected by propranolol and exacerbated by oxprenolol. The results of this study suggest that oxprenolol and propranolol influence ischemic damage to differing extents and that this difference is due to partial agonist activity. Also, the protective action of all beta-blocking compounds depends greatly on the background level of sympathetic drive.

Animals↗
PubMed1983

Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function.

The effects of intravenous amrinone on resting haemodynamic function were investigated in 15 patients with impaired left ventricular function. All patients received 1 X 5 mg/kg and 10 received a further 2 mg/kg. We observed dose related increases in heart rate and cardiac index, and reductions in mean arterial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance. A small reduction in left ventricular end-diastolic volume and a 36% increase in ejection fraction occurred. No significant change in max dp/dt, min dp/dt, (Max dp/dt/P), max (dp/dt/P), KVmax or the ratio of left ventricular end-systolic pressure to left ventricular end-systolic volume was detected. It is concluded that the beneficial effects of intravenous amrinone on the resting haemodynamics in our patients were attributable to vasodilatation, with the drug having no demonstrable positive inotropic effect.

Adult↗
PubMed1983

Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after the administration of propranolol or verapamil.

Adult↗
PubMed1982

Effects of early administration of a highly purified hyaluronidase preparation (GL enzyme) on myocardial infarct size.

79 patients with suspected myocardial infarction entered a randomised trial to establish the safety of early intravenous administration of a highly purified hyaluronidase preparation (GL enzyme) and to assess its effects on eventual infarct size as measured by electrocardiographic, enzymatic, and scintigraphic criteria. Of the 71 patients with infarction, 35 received GL enzyme and 36 placebo within 6 h of the onset of chest pain. GL enzyme injected into a peripheral vein produced no adverse changes in the clinical, haemodynamic, biochemical, or haematological variables studied. GL enzyme reduced precordial electrocardiographic indices of infarct size as reflected by a diminution (p less than 0.02) in the degree of both R wave loss and Q wave development. In addition, the number of leads developing pathological Q waves (N delta Q greater than or equal to 2), a sign of progression from ischaemia to necrosis, was reduced (p less than 0.05) after GL enzyme treatment. However, there were no significant differences in infarct size as measured by cumulative creatine kinase MB isoenzyme release or technetium-99m pyrophosphate scintigraphic infarct area, or in clinical outcome during the hospital stay. Interpretation of the enzymatic and scintigraphic data was complicated by chance bias in pre-treatment randomisation which resulted in more (p less than 0.05) patients with severe haemodynamic impairment (and hence probably larger infarct sizes) entering the GL enzyme group. Nonetheless, a favourable effect of GL enzyme on infarct size was demonstrated by precordial electrocardiographic QRS mapping, here each patient acts as his or her own control.

Clinical Trials as Topic↗
PubMed1982

Direct measurement of hepatic extraction of chenodeoxycholic acid and ursodeoxycholic acid in man.

1. The hepatic extraction ratios of chenodeoxycholic acid and ursodeoxycholic acid have been measured in 12 patients without, and 20 patients with, liver disease. 2. Ten of the patients without liver disease were studied during cardiac catheterization, with a continuous infusion technique. Two of the patients without liver disease and all those with liver disease received an intravenous bolus of [14C]chenodeoxycholic acid or [14C]ursodeoxycholic acid, during transvenous liver biopsy. 3. The extraction ratio of chenodeoxycholic acid was 0.63 +/- 0.03 (mean +/- mean +/- SEM) and of ursodeoxycholic acid 0.53 +/- 0.01, in the patients without liver disease. In those with mild liver disease, extraction was slightly impaired (chenodeoxycholic acid; 0.49 +/0 0.03; ursodeoxycholic acid: 0.43 +/- 0.05), whereas in those with more severe liver disease it was greatly reduced (chenodeoxycholic acid: 0.16 +/- 0.08; ursodeoxycholic acid: 0.07 +/- 0.01). 4. The results suggest that (a) direct measurements confirm the accuracy of indirect estimates of hepatic extraction of chenodeoxycholic acid, (b) hepatic extraction of chenodeoxycholic acid is lower than that of cholic acid and glycocholic acid, but higher than that of ursodeoxycholic acid, (c) progressive impairment of the extraction ratios of these two bile acids occurs as the severity of liver disease increases, and (d) the ratios are correlated with indocyanine green extraction ratios.

Adult↗
PubMed1982

Metabolic effects of substrates on the isolated guinea-pig heart in relation to arrhythmias during reperfusion.

Mechanisms whereby glucose reduces the incidence of pyruvate induced reperfusion arrhythmias in isolated guinea-pig hearts have been investigated. Alterations in cytoplasmic ATP/ADP ratios, creatine phosphate and glycogen were excluded as possible mechanisms. Likewise, data are presented that appear to be at variance with the proposition that glycolytically derived ATP may play a special role in the maintenance of electrical stability. To explain the anti-arrhythmic effects of glucose in terms of this thesis it is necessary to invoke compartmentation of glycolysis. A correlation between the incidence of arrhythmias and glycolytic ATP production can only exist if the contributions to glycolytic flux from glucose and glycogen utilisation can be regarded as separate.

Adenosine Triphosphate↗