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Biomedical subjects

H F Hardman

Publications and source records attributed to H F Hardman.

At least 37 records · Page 2Linked to original sources
PubMed1980

Protection of ischemic myocardium: comparison of effects of propranolol, bevantolol and N-dimethyl propranolol on infarct size following coronary artery occlusion in anesthetized dogs.

The relative extent of myocardial infarction produced by occlusion of the left anterior descendens coronary artery in anesthetized dogs was determined under control conditions or following treatment (4 h after ligation) with propranolol (1 mg/kg), bevantolol (3 mg/kg) or N-dimethyl propranolol (10 mg/kg). Doses of drugs were selected to provide similar reductions in heart rate, aortic blood pressure and contractility. Infarct size was estimated indirectly from levels of plasma creatine phosphokinase and measured histochemically by nitroblue tetrazolium stain. A significant ( p < 0.001) correlation between methods was found. Propranolol and bevantolol (beta adrenergic antagonists) produced a significant (p < 0.05) reduction (approximately 50% decrease) in infarct size, measured at 8 h following induction of ischemia, while N-dimemthyl propranolol (no beta antagonist activity) produced no effect. While all three agents produced similar hemodynamic actions and thereby reduced primary determinants of myocardial oxygen demand, only the beta blockers were able to afford protection of ischemic myocardium.

Adrenergic beta-Antagonists↗
PubMed1978

Effect of propranolol and nitroglycerin plus methoxamine on transmural creatine kinase activity after acute coronary occlusion.

Transmural creatine kinase activity was determined 5 hours after acute occlusion of the left anterior descending coronary artery in 27 open chest anesthetized dogs. In seven dogs, propranolol, 2 mg/kg, was given intravenously over a 10 minute period 10 minutes after occlusion. In 10 dogs, nitroglycerin, 300 microgram/min, was infused intravenously for 1 hour 10 minutes after occlusion. Methoxamine, 300 to 500 microgram, was administered to return blood pressure and heart rate to prenitroglycerin levels. In untreated dogs, there was a distinct transmural gradient of creatine kinase activity in the ischemic region from subepicardium to subendocardium: nonischemic subepicardium 1,187 +/- 50 international units (IU)/g versus ischemic subepicardium 1,054 +/- 46 IU/g and nonischemic subendocardium 1,170 +/- 53 IU/g versus ischemic subendocard;um 766 +/- 42 IU/g, respectively. Administration of propranolol did not affect the transmural creatine kinase gradient after 5 hours of occlusion. In contrast, nitroglycerin plus methoxamine significantly (P less than 0.05) decreased subendocardial creatine kinase depletion after 5 hours of occlusion (776 +/- 42 versus 978 +/- 47 IU/g). These findings demonstrate the unique capability of nitroglycerin plus methoxamine to protect the subendocardium during ischemic insult.

Acute Disease↗
PubMed1978

Transmural triglycerides in acute myocardial ischaemia.

The effect of coronary artery occlusion on endogenous triglycerides of left ventricular subepicardium and subendocardium was studied in the open-chest anaesthetised dog. Under control conditions, the subepicardium was found to have a greater concentration of triglycerides than the subendocardium. Thirty minutes after acute coronary artery occlusion there was a decrease followed by a steady increase at 60, 120, and 240 min in subepicardial triglycerides of the ischaemic region. No change in triglycerides in the subendocardium of normal or ischaemic regions was observed. The initial decrease of subepicardial triglycerides in the ischaemic region was blocked by administration of propranolol or bevantolol (CI-775; a specific beta 1 antagonist) given 30 min before occlusion. It is concluded that the effect of coronary artery ligation on transmural endogenous triglycerides is biphasic with an initial period of increased mobilisation followed by a period of increased deposition.

Animals↗
PubMed1978

Beneficial actions of N-dimethyl propranolol on myocardial oxygen balance and transmural perfusion gradients distal to a severe coronary artery stenosis in the canine heart.

The purpose of the present study was to compare the effects of N-dimethyl propranolol (DMP), the quaternary derivative of propranolol, and propranolol on the transmural distribution (endo/epi) of coronary blood flow in normal and ischemic regions of the myocardium. The distribution of blood flow between subendocardium and subepicardium of a nonischemic region and one distal to a severe left circumflex coronary artery stenosis was determined by use of tracer microspheres (15 microgram) in intact dog hearts. DMP (1,5 and 10 mg/kg I.V.) produced a small dose-related increase in endo/epi of the nonischemic region (1.15 +/- 0.04--1.24 +/- 0.05), whereas a larger increase was observed in the ischemic region (0.61 +/- 0.08--1.09 +/- 0.10). DMP also produced a significant increase in ischemic subendocardial blood flow (0.59 +/- 0.12--0.76 +/- 0.11 ml/min/g). Similarly, propranolol (0.5 and 1.0 mg/kg I.V.) produced a small increase in endo/epi of the nonischemic region (1.18 +/- 0.08--1.30 +/- 0.07) and a larger increase in the ischemic region (0.72 +/- 0.17--1.18 +/- 0.09). However, propranolol did not increase ischemic subendocardial blood flow. It is concluded that DMP may be an alternative to propranolol in certain types of acute myocardial ischemia when beta-adrenergic blockade is undesirable.

Animals↗
PubMed1977

The effect of ouabain on nutritional circulation and regional myocardial blood flow.

The effect of ouabain on myocardial nutritional circulation (rubidium-86 extraction) and regional myocardial blood flow (radioactive microspheres) was studied in the isolated supported canine heart preparation perfused at a constant coronary blood flow. Ouanbain (25 mug per kilogram, intravenously) produced a significant increase in mycocardial contractile force, peak left ventricular systolic pressure, and myocardial oxygen consumption. Ouabain also decreased rubidium-86 extraction (E86RB), rubidium-86 clearance (C86Rb), and the capillary transport coefficient (PS). Intracoronary infusion of ouabain (10 mug per minute) produced significant increases in contractile force (25,50, and 100 per cent above control), left ventricular systolic pressure, myocardial oxgen consumption, and the epicardial-endocardial blood flow ratio (epi/endo) of the left ventricle. When left ventricular systolic pressure was held constant (100 mm. Hg), ouabain infusion (10 mug per minute, intracoronary) increased myocardial contractile force (25,50, and 100 per cent above control) and myocardial oxygen consumption but did not change the epi/endo of the left ventricle. These results suggest that ouabain reduces E86Rb, C86Rb, and PS by producing a shunting of blood flow from endocardium to epicardium in the left ventricle. The increase in left ventricular systolic pressure appears to be responsible for these changes.

Angina Pectoris↗
PubMed1977

Effect of ortho-iodo sodium benzoate on hemoglobin-oxygen affinity in normal and ischemic myocardium.

The effect of ortho-iodo sodium benzoate (OISB) on the oxyhemoglobin dissociation curve of coronary venous blood was studied in an isolated canine heart preparation perfused at a constant coronary blood flow. Changes in P-50 (millimeters of mercury) [the oxygen tension (pO2) at which hemoglobin is 50% saturated], were used to express hemoglobin-oxygen affinity. Intracoronary infusion of OISB (200, 400 and 800 mg/min) produced a dose-related increase in coronary venous P-50 and a concurrent increase in coronary venous pO2. In addition, OISB produced a significant decrease in heart rate and increase in coronary artery perfusion pressure. During cardiac pacing at 150, 190 and 230 beats/min, OISB (400 mg/min) significantly increased coronary venous P-50, myocardial oxygen exrraction (O2E) and oxygen consumption (MVO2) whereas coronary venous PO2 was not changed. Furthermore, a 5-minute intracoronary infusion of OISB (200 mg/min) during myocardial ischemia produced an increase in O2E, MVO2 and myocardial contractility with little change in coronary venous pO2. These results suggest that acute pharmacological manipulation of the oxyhemoglobin dissociation curve may enhance oxygen release to the myocardium while maintaining the effective driving pressure (as reflected in coronary venous pO2) for diffusion of oxygen to the myocardium.

Animals↗
PubMed1976

Effect of propranolol and nitroglycerin on hemoglobin--oxygen affinity.

The effect of propranolol on the oxyhemoglobin dissociation curve (P-50) of coronary venous blood was studied in isolated canine hearts. I.v. administration of propranolol (0.5, 5.0 mg/kg) produced no significant change in P-50 over 4 hr. Following propranolol, an intracoronary infusion of nitroglycerin (10 mug/min) increased P-50. Addition of propranolol (5 X 10(-5) M to 1 X 10(-4)M) to central venous blood in vitro produced a significant increase in P-50. These data indicate that propranolol increases P-50 in vitro but does not increase P-50 in vivo, whereas nitroglycerin increases P-50 In vivo but not in vitro.

Animals↗
PubMed1976

Adenosine on myocardial oxygen consumption.

1 A 3 min intracoronary infusion of adenosine (50 mug/min) produced a significant decrease in coronary artery perfusion pressure, left ventricular systolic pressure and myocardial O2 consumption in the isolated supported heart preparation of the dog perfused at a constant coronary blood flow. Heart rate was controlled at 150, 190 or 230 beats/minute. 2 Myocardial contractile force and maximal left ventricular dp/dt were not changed by adenosine infusion. 3 The absolute decrease in myocardial O2 consumption was greater at increasing heart rates whereas the decrease in coronary artery perfusion pressure and peak left ventricular systolic pressure were similar. 4 The results suggest that the reduction in myocardial O2 consumption produced by adenosine is not related to coronary vasodilatation or to a negative chronotropic or inotropic action, but may be due to a functional shunting of blood flow from high O2 extracting regions of the myocardium to low O2 extracting ones and/or important effects on myocardial substrate utilization.

Adenosine↗
PubMed1976

Effect of adenosine on myocardial oxygen balance.

The present study was designed to determine the effect of adenosine on oxyhemoglobin equilibrium (P-50) and myocardial oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. Heart rate was controlled at 150 beats/min. A-3-minute intracoronary infusion of adenosine (10, 50 and 100 mug/min) produced significant decreases in MVO2, whereas coronary venous P-50 did not change. Adenosine-5'-monophosphate (5'-AMP) infusion (70 and 140 mug/min) did not produce a significant change in MVO2. Both adenosine and 5'-AMP caused equivalent decreases in coronary artery perfusion pressure and peak left ventricular systolic pressure. Furthermore, adenosine (50 and 100 mug/min) produced a significant decrease in MVO2 of the isolated supported fibrillating heart. These results suggest that the reduction in MVO2 observed with adenosine is not related to coronary vasodilation or to a negative inotropic or chronotropic action. Theophylline (2.5 mg/kg) partially blocked the hemodynamic effects of adenosine while completely abolishing the decrease in MVO2. Neither inosine nor hypoxanthine (50 and 100 mug/min) changed MVO2, P-50 or myocardial hemodynamics. Thus, in addition to its proposed role in coronary blood flow regulation, adenosine appears to exert important effects on myocardial metabolism.

Adenosine↗
PubMed1976

The isolated supported canine heart: a model for the evaluation of drug effects on regional myocardial blood flow.

The effect of independently varying heart rate, left ventricular systolic pressure, coronary blood flow or coronary artery perfusion pressure on the transmural distribution of myocardial blood flow was determined in the isolated supported dog heart preparation by use of radioactive microspheres. The distribution of radioactivity was expressed as the epicardial/endocardial blood flow ratio (epi/endo). At a constant coronary blood flow, increases in heart rate (111-250 beats/min) or decreases in coronary artery perfusion pressure (100-46 mm Hg) resulted in an elevation of epi/endo (0.64 to 1.12 and 0.71 to 1.41, respectively). Increasing coronary artery perfusion pressure (40-130 mm Hg) and coronary blood flow from low values resulted in a decreased epi/endo (1.28 to 0.76). The absolute level of coronary blood flow had no direct effect on epi/endo but acted through changes in coronary artery perfusion pressure. The major physiological determinants of intramyocardial blood flow distribution in the isolated dog heart are coronary artery perfusion pressure and heart rate, whereas left ventricular systolic pressure and coronary blood flow are of minor importance. An equation was developed relating the mean epi/endo of the left ventricle to hemodynamic factors studied, and a highly significant correlation was found between predicted and experimental ratios. These results indicate the potential usefulness of this model for predicting epicardial-endocardial blood flow ratios based upon drug-induced changes in hemodynamic parameters.

Animals↗
PubMed1976

Effect of propranolol on regional myocardial blood flow and oxygen consumption.

The present investigation was designed to determine the effect of propranolol on regional myocardial blood flow and oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. The transmural distribution of blood flow, determined by the radioactive microsphere technique, was expressed as the epicardial/endocardial blood flow ratio (epi/endo). Propranolol (0.5 mg/kg i.v.) produced a significant decrease in heart rate and myocardial contractile force and an increase in coronary artery perfusion pressure due to an increase in coronary vascular resistance. These hemodynamic changes were accompanied by significant decreases in epi/endo (increased endocardial perfusion) and MVO2. Reduction of perfusion pressure to control by a decrease in total coronary blood flow produced no further change in epi/endo or MVO2. However, increasing heart rate to control increased epi/endo to predrug levels. Contractile force and MVO2 remained reduced below control. Norepinephrine infusion (1 mug/min intracoronary) produced a significant increase in heart rate and contractile force and decrease in perfusion pressure. These changes were accompanied by an increase in epi/endo and MVO2. Propranolol (0.5 mg/kg i.v.) abolished the response to norepinephrine. Propranolol may produce beneficial effects in angina pectoris by a decrease in epi/endo (via a reduction in heart rate) and MVO2 and by beta adrenergic blockade of the deleterious effects of catecholamines.

Animals↗
PubMed1975

Effect of right atrial pacing and nitroglycerin on myocardial oxygen balance.

The direct effects or right atrial pacing and nitroglycerin on myocardial oxygen balance were studied in isolated canine hearts. Whereas atrial pacing produced an increase in myocardial oxygen consumption (MVO2) and no change in the affinity of hemoglobin for oxygen (P-50), an intracoronary infusion of nitroglycerin decreased both MVO2 and the affinity of hemoglobin for oxygen (increased P-50) in coronary venous blood. Under conditions of a constant coronary blood flow, nitroglycerin may benefit a hypoxic myocardium by reducing oxygen demand and by increasing availability of oxygen for rapid diffusion to tissue by increasing P-50.

Animals↗
PubMed1975

Myocardial distribution of coronary blood flow in the isolated supported heart preparation.

The regional distribution of myocardial blood flow was studied by use of radioactive microspheres (15 micro-meters [mum]) under control conditions and during an intracoronary infusion of norepinephrine (2mug/min). In control experiments endocardial blood flow was generally greater than epicardial flow; during administration of norepinephrine the endocardium received significantly less blood flow. It is proposed that normally the endocardium is well perfused, but under conditions of stress, eg, norepinephrine infusion in the presence of a constant coronary blood flow, decreased endocardial blood flow results.

Animals↗
PubMed1975

Alteration in oxyhemoglobin equilibrium (P-50) and myocardial oxygen consumption (MVO2) by nitroglycerin (GTN).

In the isolated supported dog heart preparation perfused at a constant coronary blood flow, heart rate and left ventricular systolic pressure were not changed significantly by a 3-minute intracoronary infusion of nitroglycerin (5 and 10 mug/min). Nitroglycerin produced a significant increase in coronary venous pO2 and coronary venous P-50. These effects were accompanied by a significant decrease in myocardial oxygen consumption (MVO2). An infusion of dipyridamole (25 and 50 mug/min) did not produce significant changes in coronary venous pO2, P-50 or MVO2. Both drugs produced equivalent decreases in coronary artery perfusion pressure which suggests that the increase in coronary venous P-50 or reduction in MVO2 observed with nitroglycerin is not related to coronary vasodilation. The increase in P-50 induced by nitroglycerin was not accompanied by an increase in total erythrocytic 2,3-diphosphoglycerate and was not observed in vitro. The increase in P-50 produced by nitroglycerin provides a potential reservoir of readily diffusible oxygen that may be utilized during periods of myocardial hypoxia.

Animals↗