Biomedical subjects

B D Guth

Publications and source records attributed to B D Guth.

At least 55 records · Page 3Linked to original sources

PubMed1988

Role of calcium channel blockers in experimental exercise-induced ischemia.

Calcium channel blockers, which induce vasodilation by relaxing vascular smooth muscle cells, have proven effective in the treatment of angina pectoris. To study mechanisms of calcium blockade in ischemic heart disease, conscious chronically instrumented dogs with a single coronary artery ameroid constrictor were studied during steady-state treadmill runs which induced regional myocardial ischemia. During exercise-induced ischemia, regional systolic wall thickening and subendocardial blood flow were both significantly reduced in the ischemic zone. Calcium channel blockade with verapamil, diltiazem, or nifedipine enhanced regional systolic wall thickening. Regional subendocardial blood flow in the ischemic region, measured during diltiazem and nifedipine experiments, improved during exercise. Reduced coronary artery resistance in the native vessels and/or recruitment of collaterals appears to largely explain the increased total myocardial blood supply in the jeopardized area and the increased function. However, after diltiazem, reduced exercise heart rates as well as reduced left ventricular end-diastolic pressure also contributed to the improvement in the oxygen-supply imbalance in the ischemic myocardium. These data provide a basis for understanding the efficacy of calcium channel blocker treatment in patients with coronary artery disease.

Animals↗

PubMed1988

Early diastolic filling dynamics during experimental mitral regurgitation in the conscious dog.

Diastolic flow into the left ventricle during mitral regurgitation must increase as total stroke volume increases in response to the volume overload. The mechanisms that allow augmented diastolic filling are not fully defined. Accordingly, the left ventricle of five dogs was instrumented with a micromanometer and sonomicrometers and studied during the conscious state before (control) and after the creation of significant mitral regurgitation. Serial measurements were made at control and up to 4 weeks after the creation of the volume overload. Heart rate, peak systolic wall stress, and peak positive dP/dt showed no significant changes between control and subsequent observations. End-diastolic volume and total stroke volume progressively and significantly increased during the 4-week course. When compared with the control state (51 +/- 4, mean +/- SD), the filling fraction during the first 40% of diastolic time was increased at 4 days (67 +/- 10%, p less than 0.001), 2 weeks (72 +/- 6%, p less than 0.001), and 4 weeks (76 +/- 10%, p less than 0.001). During the period of adaptation to the volume overload, filling fraction correlated with end-diastolic volume (r = 0.52, p less than 0.02) and total stroke volume (r = 0.80, p less than 0.001). Compared with the control state (0.81 +/- 0.04), eccentricity of the left ventricle at end systole decreased at 4 weeks (0.79 +/- 0.06, p less than 0.05); the absolute change in this ratio during the first 40% of diastolic time was significantly augmented at 2 weeks (0.09 +/- 0.02, p less than 0.05) and 4 weeks (0.11 +/- 0.04, p less than 0.005) compared with control (0.05 +/- 0.02). Ventricular elastance (pressure/volume) at end systole (minimum volume) was 1.70 +/- 0.50 mm Hg/ml at control, 1.09 +/- 0.46 at 4 days (p less than 0.05), 0.96 +/- 0.42 at 2 weeks (p less than 0.01), and 0.99 +/- 0.22 at 4 weeks (p less than 0.01). Moreover, the elastance change during the rapid-filling phase was significantly diminished after creation of mitral regurgitation. Thus, during the volume overload of mitral regurgitation, the left ventricle accommodates a higher percentage of its total stroke volume during early diastole; this adaptation can be correlated with augmented systolic shortening, and thereby with increased restorative forces or elastic recoil, and with reduced chamber elastance and eccentricity during the early part of diastole. Other potential mechanisms include altered systolic and relaxation loading, augmented elastic recoil of the left atrium, left atrium and left ventricular pressure gradient, accelerated myocardial inactivation, and increased adrenergic stimulation.

Animals↗

PubMed1988

Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise.

Studies on the role of alpha-adrenergic constrictor tone in the coronary vascular bed during ischemia were performed in dogs running on a treadmill. The animals were instrumented with a left ventricular pressure transducer, and regional systolic wall thickening (%WTh) was assessed by sonomicrometry in the anterior and posterior walls of the left ventricle. An intracoronary catheter was implanted chronically in the circumflex coronary artery, and a hydraulic cuff was placed proximally around the artery. After beta-adrenergic blockade with propranolol (0.8 mg/kg i.v.), acute stenosis of the coronary artery was performed during running in five dogs to induce severe regional myocardial dysfunction in the posterior wall. Intracoronary infusion of the selective alpha 2-adrenergic blocking agent idazoxan (80 micrograms/kg) improved %WTh in the ischemic region from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.05), without any significant effect on the anterior wall. Blood flow to the subendocardium of the posterior wall (radioactive microspheres) increased from 0.17 +/- 0.05 to 0.45 +/- 0.30 (ml/min)/g (p less than 0.05). It is concluded that in exercising dogs subjected to beta-adrenergic blockade, significant postjunctional alpha 2-adrenergic receptor-mediated coronary vasoconstriction exists, even during severe ischemia. Regional alpha 2-adrenergic receptor blockade can reduce regional ischemia and improve contractile function by attenuating exercise-induced sympathetic vasoconstriction in this conscious animal model.

Adrenergic alpha-Antagonists↗

PubMed1988

Temporal Fourier transform of digital angiograms for left ventricular regional wall motion analysis.

To determine whether or not the first harmonic of a temporal Fourier transform, applied pixel-by-pixel on time-intensity curves, can detect the subtle wall motion abnormalities due to ischemia, 6 dogs were instrumented with a micromanometer in the left ventricles, a hydraulic cuff occluder around the circumflex coronary artery, and sonomicrometers on the inferior (ischemic) and anterior (non-ischemic) walls. Left ventricular images, obtained after contrast injection via the pulmonary artery, were compared with dimension signals in control and 3 progressive levels of coronary stenosis (Stenosis I, II and III). Normalized, digital functional images (512 x 512 matrix, 256 shades of gray/pixel) were divided into anterior, apical, and inferior areas to acquire regional mean phase (degrees) and amplitude (intensity units) values. After inducing stenosis, phase in ischemic region significantly increased at all 3 levels of stenosis, whereas amplitude significantly decreased at Stenosis II and III. However, amplitude images showed clearly the topographic site of ischemia. There was a progressive increase in phase and decrease in amplitude in ischemic areas as the percent wall thickening (%WTh) fell (phase vs. %WTh: r = -0.55, p less than 0.005; amplitude vs. %WTh: r = 0.71, p less than 0.001). Heart rate and peak systolic pressure showed no significant changes during stenosis. We conclude that quantitative functional images, generated from a temporal Fourier transform, are sensitive to the detection of left ventricular regional wall motion abnormalities during mild, moderate, and severe degrees of ischemia.

Animals↗

PubMed1988

Decreased regional contractility in nonischemic myocardium during acute coronary artery occlusion in conscious pigs.

The purpose of this study was to use the relationship between end-systolic left ventricular pressure and segment length to assess the inotropic state of nonischemic myocardium during acute coronary artery occlusion in the conscious pig. Eight pigs were chronically instrumented with sonomicrometers to measure midwall segmental shortening and a micromanometer to measure left ventricular pressure. Occlusion of the inferior vena cava with a pneumatic occlusive cuff caused transient decreases in left ventricular pressure so that the relationship of left ventricular pressure and segment length at end systole could be determined over a range of pressures. In preliminary studies using open-chest pigs, this relation was shown to be highly linear and best quantified using a calculated segment length at a left ventricular pressure of 100 mm Hg (ESL100). During acute, 1-min occlusion of the left anterior descending coronary artery, the ESL100 of the nonischemic lateral and posterior walls was significantly increased from 8.75 +/- .18 mm to 9.64 +/- .21 mm (mean +/- SD, p less than .01), indicating a decreased inotropic state. Similarly, during occlusion of the left circumflex coronary artery, the ESL100 of the nonischemic anterior wall increased from 8.44 +/- 2.53 mm to 9.26 +/- 3.12 mm (p less than .05). This was not associated with a change in the amount of shortening during systole. Pharmacological autonomic blockade using atropine and propranolol failed to alter the response of nonischemic zones to acute coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Ischemic myocardial dysfunction assessed by temporal Fourier transform of regional myocardial wall thickening.

A Fourier analysis including the first 20 harmonics was performed on sonomicrometric measurements of regional myocardial wall thickness in eight conscious dogs under control conditions and at four levels of ischemia produced by a hydraulic occluder on the left circumflex coronary artery. Systolic wall thickening was reduced from 26.47 +/- 6.20% (S.D.) (control) to 22.05 +/- 5.73% (mild stenosis), 17.00 +/- 5.86% (moderate stenosis), 11.46 +/- 3.56% (severe stenosis), and 3.69 +/- 2.57% (30-second occlusion), values significantly different from each other (p less than 0.01). The amplitude of the first harmonic decreased stepwise from 1.35 +/- 0.31 to 1.08 +/- 0.29 mm, 0.90 +/- 0.27 mm, 0.69 +/- 0.24 mm, and 0.43 +/- 0.12 mm, all significantly different from each other (p less than 0.05). These amplitude values correlated to percent systolic wall thickening (r = 0.894, p = 0.001). A phase shift of the first harmonic from 137 +/- 11 to 139 +/- 14 degrees, 150 +/- 15 degrees (p less than 0.05 vs control), 161 +/- 21 degrees (p less than 0.01 vs control), and 191 +/- 21 degrees (p less than 0.01 vs control and severe stenosis) correlated with the increase in time from end diastole to the point of maximum wall excursion (r = 0.662, p less than 0.001). These data indicate that the extent of ischemic regional myocardial hypokinesis can be adequately described by the amplitude of the first harmonic, and that the asynchrony of ventricular contraction and relaxation can be detected from the phase of the first harmonic.

Animals↗

PubMed1987

Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs.

Postreperfusion regional myocardial dysfunction may be associated with depletion of high energy phosphate compounds during ischemia and with their relatively slow repletion during reperfusion. However, few studies have correlated relatively rapid changes in regional myocardial function (sonomicrometers) and blood flow (microspheres) with high energy phosphate concentrations measured using phosphorus-31 nuclear magnetic resonance spectroscopy in intact large animal models of regional myocardial ischemia. The left anterior descending coronary artery of mongrel dogs was abruptly occluded for 17.1 +/- 1.9 minutes and then completely released; measurements were made for an additional 22 minutes. Transmural blood flow decreased from 1.07 +/- 0.25 to 0.25 +/- 0.10 ml/(min X g) and holosystolic expansion was observed in all dogs (segmental systolic shortening decreased from 9.3 +/- 3.7 to -6.3 +/- 6.0%). Phosphocreatine (PCr) measured during 4.4 minute sampling intervals decreased to steady state within the first sampling period after occlusion and was 45.9 +/- 17.0% of control at the end of the occlusion, whereas beta-adenosine triphosphate (beta-ATP) reached its lowest level early after reperfusion (72.7 +/- 13.3% of control). The ratio of PCr to inorganic phosphate (Pi) decreased during the occlusion (3.34 +/- 0.75 versus 1.01 +/- 0.61) but returned to control level early during reperfusion. The ratio of PCr to beta-ATP also decreased during coronary occlusion (2.16 +/- 0.39 versus 1.29 +/- 0.39) but did not return to control level during reperfusion. Significant correlations were observed between the intensity of ischemia (reduced blood flow) and reductions in regional contractile function, PCr, beta-ATP, myocardial pH and the increase in Pi during the coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Role of heart rate reduction in the treatment of exercise-induced myocardial ischaemia.

The role of bradycardia in reducing exercise-induced ischaemia and wall dysfunction was examined in dogs with single vessel chronic coronary artery stenosis created using an ameroid constrictor. Treadmill exercise produced significant regional myocardial ischaemia (blood flow measured using microspheres) and contractile dysfunction (systolic wall thickening measured with sonomicrometers). Dogs were initially studied during a control run before and during a second identical run after administration of the cardioselective beta-adrenergic blocker atenolol, which improved regional ischaemic function from 4.4 +/- 3.7% to 8.5 +/- 2.8% and subendocardial perfusion from 0.43 +/- 0.23 to 0.55 +/- 0.29 ml min-1 g-1. In another group of dogs during a run with atenolol, the heart rate was paced to match the rate observed in the control run. During the atenolol run with pacing, all beneficial effects of atenolol observed at the reduced exercise heart rate were lost. A third group of dogs received the bradycardic agent UL-FS 49 (1.0 mg kg-1, i.v.) prior to exercise. UL-FS 49 produced a heart rate reduction during exercise from 230 +/- 19 to 139 +/- 10 beats min-1; this was associated with an increase in systolic wall thickening from 9.3 +/- 5.0% (during the control run) to 21.5 +/- 8.4%, thereby eliminating the exercise-induced contractile dysfunction. Transmural myocardial blood flow per beat to the poststenotic myocardium was improved significantly from 4.8 X 10(-3) +/- 1.9 X 10(-3) ml beat-1 to 9.8 X 10(-3) +/- 1.7 X 10(-3). Atrial pacing to match heart rate to the control exercise rate during the UL-FS 49 run did not eliminate all of the improvement in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Contractile responses to sympathetic activation after coronary instrumentation.

The consequences of acute coronary dissection and chronic coronary instrumentation on contractile responses to sympathetic activation were examined in dogs. Stimulation of the left ventrolateral cervical cardiac nerve in seven anesthetized dogs after acute dissection of the left circumflex coronary artery (CX) did not change the increase in systolic shortening velocity. After acute dissection of the left anterior descending coronary artery (LAD), nerve stimulation increased shortening velocity of the posterior wall in all dogs but enhanced that of the anterior wall in only five dogs. In six conscious dogs with chronic instrumentation of the CX, reflex sympathetic activation induced by occlusion of the inferior vena cava comparably increased thickening velocities of both the anterior wall and posterior walls both at 1 and 3 wk after instrumentation. In six other dogs with chronic instrumentation of the LAD, responses to caval occlusion were nonuniform and correlated to the morphological degree of sympathetic denervation. Therefore, acute dissection and chronic instrumentation of the LAD may produce sympathetic denervation but do not cause functionally significant sympathetic denervation of the CX region.

Animals↗

PubMed1987

Effects of left circumflex Ameroid constrictor placement on adrenergic innervation of myocardium.

We evaluated the adrenergic innervation of the swine and canine myocardium after placement of an Ameroid constrictor around the left circumflex coronary artery (LCX). Fluorescent histochemistry was used to identify adrenergic nerve terminals in the myocardium and coronary vasculature. Ameroid occlusion of the proximal LCX in 10 pigs for 3 wk resulted in 6 +/- 1% infarction as well as myocardial ischemia in the left circumflex region of pigs studied during exercise. However, placement of the Ameroid constrictor did not significantly alter the surface density of the nerve terminals in the LCX region of myocardium when compared with innervation of control hearts. Histological examination of the coronary arterial adrenergic innervation in Ameroid-occluded pigs revealed that coronary vessels in the circumflex region of the heart were innervated. Similarly, in seven LCX Ameroid-occluded dogs, no significant decrease in adrenergic innervation of the LCX region of myocardium was observed when compared with control dogs. In contrast LCX Ameroid-occluded pigs demonstrated significant (P less than 0.01) denervation of the left anterior descending (LAD) region of myocardium when compared with control animals. The close proximity of adrenergic nerve bundles in the proximal LAD region indicates that denervation of the myocardium supplied by the LAD may result from the dissection and/or fibrosis associated with placement of the Ameroid constrictor on the proximal LCX. Our results suggest that placement of an Ameroid constrictor on the proximal LCX does not significantly alter the adrenergic innervation of the LCX-perfused myocardium or its associated coronary vasculature. However, denervation of LAD-perfused myocardium and its vasculature may result.

Adrenergic Fibers↗

PubMed1987

Adaptation of the left ventricle to exercise-induced hypertrophy.

Cardiac functional and structural adaptations to exercise-induced hypertrophy were studied in 68 pigs. Pigs were exercise trained on a treadmill for 10 wk. Sequential measurements were made of cardiac dimensions, [left ventricular end-diastolic diameter (EDD), changes in diameter (delta D%), wall thickness (WTh), wall thickening (WTh%), left ventricular pressure (LVP), time derivative of pressure (dP/dt), stroke volume, total body O2 consumption (VO2), blood gases, and systemic hemodynamics] at rest and during moderate and severe exercise. Postmortem studies included morphometric measurements of capillary density, arteriolar density, mitochondria, and myofibrils. All of the exercise-trained pigs showed significant increases in aerobic capacity. Maximum O2 consumption (VO2 max) increased by 37.5% in group 1 (moderate exercise training) and 34% in group 3 (heavy exercise training). Cardiac hypertrophy ranged from less than 15% in a group (n = 8) subjected to moderate exercise training to greater than 30% in a group (n = 11) subjected to heavy exercise training. Before training, exercise was characterized by a decreasing EDD during progressive exercise; this was reversed after exercise training. Stroke volume and end-diastolic volumes during exercise showed a highly significant increase after exercise training and hypertrophy. Morphometric measurements showed that mitochondria and cell membranes increased with increasing myocyte growth in all exercise groups, but there was only a partially compensated adaptation of capillary proliferation. Arteriolar number and length increased in all exercise groups. Intrinsic contractility as measured by delta D%, WTh%, or left ventricular dP/dt did not increase with exercise training and in some instances decreased. Therefore, left ventricular adaptation to strenuous exercise in the pig heart is primarily one of changes in left ventricular dimensions and a compensated hypertrophy. Exercise-induced increases in EDD and stroke volume can be accounted for by decreases in peripheral resistance and increased cardiac dimensions.

Acclimatization↗

PubMed1987

Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.

There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.

Animals↗

PubMed1987

Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis.

We have previously demonstrated that the beneficial effect of cardioselective beta-blockade on exercise-induced ischemia is due entirely to negative chronotropism. Therefore we studied the effect of a new bradycardiac agent (UL-FS 49) in 10 dogs with chronic coronary artery stenosis produced by an ameroid constrictor. Regional myocardial function (sonomicrometers, wall thickness) and blood flow (microspheres) were measured during a control treadmill exercise bout and an identical run 3 hr later after the administration of UL-FS 49 (1.0 mg/kg iv). In the control run, heart rate increased from 114 +/- 20 to 230 +/- 19 beats/min and systolic wall thickening (%WT) in the poststenotic myocardium decreased from 23.3 +/- 5.2% at rest to 9.3 +/- 5.0%, a 60% reduction. Subendocardial blood flow in the ischemic area decreased from 1.04 +/- 0.30 to 0.55 +/- 0.40 ml/min/g, blood flow per beat decreased from 9.1 X 10(-3) to 2.5 X 10(-3) ml/g, and mean transmural flow failed to increase (1.06 +/- 0.30 vs 1.08 +/- 0.39 ml/min/g). During exercise with UL-FS 49, heart rate increased from 89 +/- 10 to only 139 +/- 10 beats/min. End-diastolic left ventricular pressure was increased compared with that during the control run (35.7 +/- 3.0 vs 28.9 +/- 5.5 mm Hg) but left ventricular peak systolic pressure and dP/dt were unchanged. %WT in the ischemic zone did not change significantly during exercise with UL-FS 49 (23.3 +/- 7.9% at rest, 21.5 +/- 8.4% during the run), and in the nonischemic zone it increased to the same extent as during the control run.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.

We examined the importance of decreased heart rate in the beneficial effect of beta-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3-1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 +/- 25 beats per minute (SD, n = 9) to 166 +/- 15, and ischemic zone wall thickening during systole improved from 27 +/- 22% of the resting value in the control run to 50 +/- 25% of the resting value in the atenolol run (p less than 0.01). Atrial pacing then increased heart rate to 217 +/- 23 beats per minute, and regional wall thickening deteriorated to 15 +/- 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The effect of hemodilution with fluorocarbon or dextran on regional myocardial flow and function during acute coronary stenosis in the pig.

The effect of replacement of approximately 50% of the blood volume, in the presence of critical coronary stenosis, was investigated in anesthetized pigs. Two agents were used for replacement: 6% dextran 70 and Fluosol-DA, a fluorocarbon "blood substitute," capable of transporting oxygen by virtue of its high solubility. Critical coronary stenosis of 15-min duration was imposed on the circumflex coronary artery by means of a micrometer snare, before and after an exchange-transfusion with one of the above acellular agents, resulting in comparable reductions of myocardial blood flow (determined by microspheres) to the circumflex zone. In the ischemic zone, systolic wall-thickening (as determined by sonomicrometry) was reduced by 62 +/- 10% in the dextran-diluted pigs, but only by 33 +/- 7% in the Fluosol-diluted pigs (p less than .05). Estimated oxygen delivery-rate in this zone, during coronary constriction, was 6.2 and 7.5 ml min-1 100 g-1, respectively. Electron microscopic examination of the normally perfused zone of the heart showed no morphological change attributable to Fluosol. The findings suggest that, in the presence of critical coronary stenosis, hemodilution by Fluosol-DA can be tolerated, while similar hemodilution with dextran results in aggravation of myocardial hypoxia. In three instances, severe reactions were observed immediately following the administration of Fluosol. These were suggestive of complement-activation and were excluded from the analysis.

Animals↗

PubMed1986

Experimental exercise-induced ischemia: drug therapy can eliminate regional dysfunction and oxygen supply-demand imbalance.

The purpose of this study was to test the hypothesis that moderately severe exercise-induced regional myocardial ischemia can be prevented by combined pharmacologic intervention. Eight chronically instrumented dogs were studied using an ameroid constrictor to produce critical stenosis of the left circumflex coronary artery. The dogs were studied during steady state treadmill exercise that induced regional myocardial dysfunction (reduced systolic wall thickening; sonomicrometers) and ischemia (reduced subendocardial blood flow; microspheres). During a control exercise run, wall thickening in the ischemic posterior wall decreased from 21.4 to 13.3% whereas subendocardial blood flow failed to increase normally (36% of that in the normal zone). In the control anterior wall, both wall thickening and subendocardial blood flow increased significantly during the control run. Wall thickness-left ventricular pressure loop areas were calculated as an index of regional work; this index increased abruptly with the onset of exercise in both regions but became significantly depressed in the ischemic region during the steady state exercise. Therapy with a combination of atenolol (0.3 mg/kg body weight orally), diltiazem (0.3 mg/kg intravenously) and isosorbide dinitrate (2.0 mg/kg orally) effectively prevented regional myocardial ischemia and regional dysfunction. After drug therapy, wall thickening in the posterior wall increased from 17.3% at rest to 18.8% during exercise, and the regional transmural blood flow pattern was markedly improved. The initial overshoot of the regional work index during exercise was blunted by the drug therapy, and at steady state no differences between the ischemic and control regions were detected. Thus, combined drug therapy can eliminate exercise-induced regional myocardial ischemic dysfunction and appears to normalize the oxygen supply-demand imbalance.

Adrenergic beta-Antagonists↗

PubMed1986

Validation of a respiratory mask for measuring gas exchange in exercising swine.

A respiratory mask was developed for resting and exercising swine. The lightweight, low-dead-space design fits airtight against the animals' snouts to provide breath-by-breath measurements of respiration and metabolism. Validation of the mask was carried out using the Fick principle with dye-dilution cardiac outputs and arterial and mixed venous O2 content measurements. Linear regression analysis of O2 consumption (VO2) measurements by the two techniques revealed a slope of 1.07 and a Y-intercept of -1.06 ml X kg-1 X min-1. The standard error of the estimate of VO2 was 3.5 ml X kg-1 X min-1. The mask design permits rapid measurements of ventilation and metabolism in response to acute and chronic exercise.

Animals↗

PubMed1986

Ischemia of the dog heart induces the appearance of a cardiac mRNA coding for a protein with migration characteristics similar to heat-shock/stress protein 71.

Recent evidence indicates that different forms of stress, including hypoxia, can induce specific proteins called heat-shock or stress proteins in various types of mammalian cells. These studies examined whether myocardial ischemia can result in increased levels of proteins with molecular weight and isoelectric point characteristics similar to those described for heat-shock or stress proteins. The left anterior descending coronary artery of the dog heart was completely occluded; normal and ischemic myocardial samples were obtained 6 hours after occlusion; and total cardiac proteins and RNA were prepared. Ribonucleic acid was translated in vitro in a modified rabbit reticulocyte lysate system, and [35S]-methionine-labelled translational products as well as unlabelled cardiac proteins were separated by two-dimensional gel electrophoresis. Total proteins were visualized by silver staining and in vitro translation products quantified by fluorometry. A translatable mRNA coding for a 71,000 dalton peptide with an isoelectric point of 5.8 was markedly increased in the ischemic myocardium after 6 hours of ischemia. A protein with similar migration characteristics was detected in ischemic myocardium but not in normal myocardium. These results indicate that an mRNA coding for a translational product with similar migration characteristics of heat-shock protein 71 is induced by ischemia in the dog heart.

Animals↗