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Biomedical subjects

R J Bache

Publications and source records attributed to R J Bache.

At least 145 records · Page 8Linked to original sources
PubMed1986

Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis.

Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventricular:body weight ratio was 7.1 +/- 0.4 as compared to 4.4 +/- 0.3 g/kg in 11 normal dogs (P less than 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 +/- 0.39) was substantially less than in normal dogs (6.19 +/- 0.54 ml/min per g; P less than 0.01), whereas minimum coronary resistance was increased from 14.1 +/- 1.7 in normal dogs to 23.7 +/- 5.4 mmHg. min X g/ml (P less than 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress.

Animals↗
PubMed1986

Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia.

To determine whether regional myocardial dysfunction occurring after exercise-induced ischemic might be caused by continued abnormalities of myocardial blood flow in the post-exercise period, nine dogs were instrumented with ultrasonic microcrystals for determination of circumferential segment shortening, circumflex artery electromagnetic flow probes, and hydraulic coronary artery occluders. Dogs performed treadmill exercise during partial inflation of the coronary artery occluder. When the stenosis was maintained after exercise (persistent stenosis), subendocardial flow = 0.79 +/- 0.42 ml/min per g vs. 1.39 +/- 0.43 ml/min per g control), and this was associated with continued dysfunction in the ischemic zone (segment shortening 45.4 +/- 36.9% of resting control). When the stenosis was released immediately after exercise (temporary stenosis), however, flow was markedly increased 1 min post-exercise (mean transmural flow 4.24 +/- 1.22 ml/min per g; subendocardial flow 4.18 +/- 1.52 ml/min per g), and this was associated with a transient increase in segment shortening to 104.5 +/- 9.3% of resting control. 5 min after exercise, however, moderate reductions in ischemic segment shortening were noted after both temporary stenosis and persistent stenosis runs, and these persisted for 30 min post-exercise. It is concluded that regional left ventricular dysfunction may persist for a significant period of time after exercise-induced ischemia. Furthermore, early after exercise, dysfunction is related to persistent abnormalities of myocardial blood flow, whereas late after exercise it is independent of primary reductions in myocardial blood flow.

Animals↗
PubMed1985

Myocardial perfusion in compensated and failing hypertrophied left ventricle.

This study examined blood flow in the hypertrophied left ventricle with and without failure. Left ventricular hypertrophy was produced in 20 dogs by banding the ascending aorta at 6-7 wk of age; studies were performed after animals reached adulthood. Sixteen dogs had compensated hypertrophy, while four dogs had cardiac failure manifested by left ventricular dilatation and end-diastolic pressures greater than 18 mmHg. The degree of hypertrophy, assessed by left ventricular-to-body weight ratio, was similar in animals with compensated hypertrophy (7.29 +/- 0.26 g/kg) and failure (8.45 +/- 0.15); both were greater than control (4.50 +/- 0.15, P less than 0.01). Left ventricular systolic pressure was similar in compensated hypertrophy (184 +/- 9 mmHg) and failure (226 +/- 29), as compared with control (130 +/- 4; P less than 0.01). Left ventricular blood flow measured with microspheres was 0.89 +/- 0.07 ml X min-1 X g-1 in control animals, was increased to 1.34 +/- 0.05 with compensated hypertrophy (P less than 0.001), and was further increased with failure to 1.86 +/- 0.40 (P less than 0.05). The left ventricular wall thickness-to-cavity diameter ratio was increased to 0.63 +/- 0.04 with compensated hypertrophy but was only 0.40 +/- 0.05 in dogs with failure (P less than 0.01), suggesting that wall stress was greater in hearts with failure. These data suggest that increased blood flow rates in dogs with failure resulted from increased myocardial O2 requirements due to increased systolic wall stress. Need for increased blood flow during resting conditions in dogs with failure would impair the ability for further coronary vasodilation during periods of cardiac stress.

Animals↗
PubMed1985

Effect of arteriolar dilation on coronary artery diameter distal to coronary stenoses.

Previous studies have suggested that worsening hemodynamic severity of coronary stenoses in response to distal arteriolar dilation may be related to dilation of the normal epicardial artery adjacent to the stenosis resulting in increasing percent stenosis. To test this hypothesis we used sonomicrometry to continuously measure external circumflex coronary artery diameter distal to snare stenoses of varying severity in 19 open-chest dogs and 5 awake, chronically instrumented dogs. Arteriolar dilation produced by release of a transient coronary occlusion or by intracoronary injection of adenosine caused a decrease in circumflex coronary diameter distal to the stenosis. Regression analysis showed that circumflex diameter and pressure distal to the stenosis were directly related (mean r: transient occlusion, 0.86 +/- 0.04; adenosine, 0.97 +/- 0.01). The close relationship between pressure and diameter suggests that the decrease in diameter in response to arteriolar dilation was a passive effect. Passive coronary narrowing distal to a stenosis suggests that a similar effect may occur within a compliant stenosis, thus partly explaining the increase in severity of compliant stenoses in response to arteriolar dilation.

Adenosine↗
PubMed1985

Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Regional function and perfusion at the lateral border of ischemic myocardium.

To determine whether function is depressed in areas of myocardium adjacent to an area of myocardial ischemia, 16 open-chest dogs were studied with both two-dimensional echocardiography and ultrasonic microcrystals. Regional myocardial blood flow was measured with radioactive microspheres during control periods and after coronary arterial ligation. Segments of myocardium adjacent to the area of ischemia were found to have no significant change in transmural blood flow (1.02 +/- 0.38 ml/g/min control vs 0.95 +/- 0.3 ml/g/min after ligation) or subendocardial flow (1.18 +/- 0.41 ml/g/min control vs. 1.19 +/- 0.37 ml/g/min after ligation). Regional function assessed echocardiographically as percent change in segment area was significantly depressed in these normally perfused adjacent areas (69.5 +/- 18.8% control vs 52.5 +/- 19.8% after ligation; p less than .01). There was a significant relationship between proximity to border of infarction and degree of adjacent dysfunction (r = .50, p less than .01 for echocardiography; r = .70, p less than .01 for ultrasonic microcrystals). It is concluded that systolic performance is depressed in nonischemic myocardium directly adjacent to the lateral border of an area of acute myocardial ischemia.

Animals↗
PubMed1984

Global left ventricular contractility in three models of hypertrophy evaluated with Emax.

Using the load independent contractility index, end-systolic pressure-volume ratio (Emax), contractility of the hypertrophied left ventricle (LV) from three different models was evaluated in conscious, resting dogs. The experimental animals included 12 dogs with perinephritic hypertension (HYP) (aortic diastolic pressure 130 +/- 5 mm Hg), 12 dogs who underwent aortic banding (AOB) at 6 to 8 weeks of age (resting aortic gradient 110 +/- 15 mm Hg), and 12 dogs with chronic fluid overload from aortocaval fistula (ACF). These were compared with 12 normal dogs (CTL). LV dimension and pressure were measured with ultrasonic tranducers and micromanometers. All three models resulted in hypertrophy with significant (P less than 0.01) increase in LV weight-to-body weight ratio (6.3 +/- 0.4, 8.4 +/- 0.5, 6.3 +/- 0.4, respectively, vs 4.4 +/- 0.1 g/kg). Cardiac output (6908 +/- 740 vs 2424 +/- 276 ml/min) and end-diastolic volume (118 +/- 11 vs 50 +/- 4 ml) were significantly (P less than 0.01) increased in AOB (18 +/- 1 vs 9 +/- 2 mm Hg). dp/dtmax was not significantly different among all groups. Emax (CTL = 5.3 +/- 0.4 mm Hg/ml) was not significantly changed in HYP (9.5 +/- 2.1) but was significantly (P less than 0.01) increased in AOB (14.1 +/- 2.6), and significantly (P less than 0.01) depressed in ACF (2.4 +/- .03). Thus, LV hypertrophy from systemic hypertension (HYP) or proximal aortic hypertension (AOB) is, at least initially, associated with preservation of contractility and normal hemodynamic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effect of beta-adrenergic blockade with timolol on myocardial blood flow during exercise after myocardial infarction in the dog.

The effect of beta-adrenergic blockade with timolol (40 micrograms/kg) on myocardial blood flow during rest and graded treadmill exercise was assessed in 12 chronically instrumented dogs 10 to 14 days after myocardial infarction was produced by acute left circumflex coronary artery occlusion. During exercise at comparable external work loads, the heart rate-systolic blood pressure product was significantly decreased after timilol, with concomitant reductions of myocardial blood flow in normal, border and central ischemic areas (p less than 0.001) and increases in subendocardial/subepicardial blood flow ratios (p less than 0.05). In addition to the blunted chronotropic response to exercise, timolol exerted an effect on myocardial blood flow that was not explained by changes in heart rate or blood pressure. At comparable rate-pressure products during exercise, total myocardial blood flow was 24% lower after timolol (p less than 0.02) and flow was redistributed from subepicardium to subendocardium in all myocardial regions. Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium.

Animals↗
PubMed1984

Effect of nifedipine on myocardial blood flow during exercise in dogs with chronic coronary artery occlusion.

The effect of nifedipine, 0.010 mg/kg intravenously, on myocardial blood flow was studied in 15 dogs 4 weeks after placement of an Ameroid constrictor on either the left circumflex or left anterior descending coronary artery to produce total coronary occlusion. Myocardial blood flow was measured with radionuclide-labeled microspheres at rest and during two levels of treadmill exercise to achieve a heart rate of 190 (light exercise) and 230 (heavy exercise) beats/min. During control conditions, increasing exercise resulted in a progressive increase in myocardial blood flow in normally perfused areas, but was associated with worsening subendocardial hypoperfusion in collateral-dependent areas. Nifedipine administration resulted in a transient reduction of arterial pressure and an increase in heart rate. To determine whether nifedipine exerted significant persistent effects on the coronary collateral circulation, measurements of myocardial blood flow were repeated beginning 30 minutes after nifedipine administration, at a time when heart rate and arterial pressure had returned to control levels. In normally perfused areas, nifedipine did not significantly alter myocardial blood flow at rest, but increased mean myocardial blood flow from 2.06 +/- 0.15 to 2.40 +/- 0.20 ml/min per g during light exercise (p less than 0.01), while blood flow during heavy exercise was not significantly altered. In collateral-dependent myocardial areas, the volume and transmural distribution of myocardial blood flow were not significantly altered after nifedipine administration either at rest or during exercise. These results fail to demonstrate persistent vasodilation of the coronary collateral vessels after the systemic hemodynamic effects of nifedipine have subsided.

Animals↗
PubMed1984

Effects of nifedipine and diltiazem on coronary reactive hyperaemia.

The effects of nifedipine and diltiazem on the reactive hyperaemic response which followed 10 s occlusions of the left circumflex coronary artery was studied in 18 chronically instrumented awake dogs. Nifedipine (0.010 mg X kg-1, iv) and diltiazem (0.30 mg X kg-1, iv) were administered to produce 2 1/2 to 3-fold peak increases in left circumflex coronary blood flow. Coronary flow returned to the control value within 30 min after drug administration, and reactive hyperaemia was examined from 30 min to 2 h after drug administration, when resting coronary blood flow, heart rate, arterial pressure and left ventricular end-diastolic pressure were not different from pretreatment values. Both nifedipine and diltiazem caused blunting of the reactive hyperaemic response following 10 s coronary occlusions with reduction of excess blood flow during reactive hyperaemia from 20.5 +/- 2.65 ml during control conditions to 11.4 +/- 3.2 ml 30 min after nifedipine (P less than 0.001), and from 21.0 +/- 3.74 ml to 13.8 +/- 3.2 ml 30 min after diltiazem (P less than 0.001). Coronary reactive hyperaemia remained depressed for 60 min after nifedipine and throughout the entire 2 h observation period after diltiazem. Measurements of myocardial blood flow with radioactive microspheres demonstrated that neither nifedipine nor diltiazem increased collateral flow during coronary occlusion. Thus, blunting of the reactive hyperaemic response could not be attributed to relief of ischaemia by enhanced collateral blood flow.

Animals↗
PubMed1984

Adrenergic coronary vasoconstriction in acute right ventricular hypertension.

This study tested the hypothesis that alpha-adrenergically mediated coronary vasoconstriction during the haemodynamic stress of right ventricular hypertension antagonises the effect of adenosine. Myocardial blood flow and plasma catecholamines were measured in 12 awake, but mildly sedated, chronically instrumented dogs during acute pulmonary artery constriction (PAC) before and during an infusion of adenosine (1 mg X kg-1 iv), with and without prior alpha blockade with phenoxybenzamine (10 mg/kg iv). PAC was performed by gradual inflation of a pulmonary artery hydraulic occluder until aortic pressure began to fall, after which aortic pressure was restored to control levels by aortic constriction. Heart rate was held constant by pacing. Two distinct patterns of response to adenosine during PAC were observed. Six dogs (group A) demonstrated attenuation of adenosine induced coronary vasodilatation; left ventricular (LV) myocardial flow fell from 7.35 +/- 1.14 ml X min-1 . g-1 (+/- SE) during adenosine to 3.63 +/- 0.81 during PAC and adenosine (p less than 0.05). In the six remaining dogs (group B) attenuation was not observed (LV flow = 6.51 +/- 0.92 during adenosine; 8.14 +/- 1.11 during PAC and adenosine). During PAC, both the severity of RV hypertension and levels of circulating catecholamines were greater in group A than in group B. Alpha-blockade partially restored adenosine responsiveness in group A during PAC, and LV flow increased to 6.23 +/- 0.80 (p less than 0.05). We propose that attenuation of the coronary flow response to adenosine infusion during PAC is related to the severity of PAC and alpha-adrenergically mediated coronary vasoconstriction.

Adenosine↗
PubMed1984

Effect of indomethacin on coronary blood flow during graded treadmill exercise in the dog.

This study tested the hypothesis that metabolites of arachidonic acid may contribute to the coronary vascular response to physiological increases of myocardial O2 consumption that occur during exercise. Studies were performed in eight chronically instrumented dogs with electromagnetic flowmeter probes on the left circumflex coronary artery and aortic and coronary sinus catheters. Data were obtained at rest and during graded treadmill exercise during control conditions and after administration of the cyclooxygenase inhibitor indomethacin. During control conditions heart rate, aortic pressure, and coronary blood flow increased progressively during exercise; this was accompanied by a significant increase in myocardial O2 extraction, as evidenced by a decrease in coronary venous O2 tension (Po2) particularly during the first stage of exercise. Indomethacin (5 mg/kg iv) resulted in marked blunting of the coronary vasodilator response to intracoronary arachidonic acid in anesthetized open-chest dogs. After administration of indomethacin to awake dogs, resting heart rate, aortic pressure, and coronary venous Po2 were unaltered, and the response of these variables to exercise was not changed. The increase in coronary blood flow during exercise was also unchanged after indomethacin, so that the relationship between myocardial O2 consumption and coronary blood flow was unaltered by cyclooxygenase inhibition. Thus we were unable to demonstrate a significant effect of the prostaglandin system in mediating the coronary vascular response to exercise.

Animals↗
PubMed1984

Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy: metabolic evidence for myocardial ischemia.

This study tested the hypothesis that in the chronically hypertrophied left ventricle pacing stress may cause abnormalities of perfusion that result in myocardial ischemia. Left ventricular hypertrophy (LVH) was produced by banding the ascending aorta of 10 dogs at 6 weeks of age, and studies were carried out after the animals had reached adulthood and when mean left ventricular/body weight ratio was 74% greater than in eight control dogs. Myocardial blood flow was measured with microspheres during pacing at 100, 200, and 250 beats/min, while aortic and coronary sinus blood samples were obtained for determination of concentrations of lactate and the adenosine metabolites inosine and hypoxanthine. In the control dogs, increasing heart rates were associated with an increase in mean myocardial blood flow while subendocardial flow was maintained at a level equal to or greater than subepicardial flow. Myocardial lactate uptake ranged from +60% to -5%, and adenosine metabolites were not detected in coronary sinus blood (less than 0.5 microM/l). In four dogs that underwent aortic banding no production of lactate or adenosine metabolites was observed at any heart rate; in these animals subendocardial flow was maintained at a level equal to or greater than subepicardial flow at all pacing rates. The remaining six dogs with LVH demonstrated net lactate production significantly greater than control during pacing at 250 beats/min; five of these six animals also produced adenosine metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1983

Decrease in thallium-201 image defect size after permanent coronary occlusion.

In the 24 hours after coronary occlusion, some defects on thallium-201 images decrease in size. This study examined the mechanism of the decrease in defect size in dogs with experimental coronary occlusion. The left anterior descending coronary artery was permanently occluded in chronically instrumented awake dogs. Myocardial blood flow was measured with radioactive microspheres immediately before occlusion, 30 minutes, and 24 hours after occlusion. Thallium-201 was injected and imaging was performed 2 to 6 days before occlusion, 30 minutes, and 24 hours after occlusion. Two dogs, in which less than 1% of the left ventricle was infarcted, had no defects on the 30-minute postocclusion images. In four dogs the thallium-201 images did not change appreciably over 24 hours (group 1), while in three dogs the image defect size decreased (group 2). In groups 1 and 2 respectively the percent increase in blood flow to the hypoperfused area was: subendocardium 9 +/- 7% vs 31 +/- 15%; subepicardium 26 +/- 6% vs 47 +/- 2% (p less than 0.05). Therefore a decrease in the size of thallium-201 image defects occurred if a sufficient increase in collateral flow to the hypoperfused area took place in the first 24 hours after coronary occlusion. The defects appeared to decrease in size even in the absence of a detectable change in the lateral borders of the hypoperfused area.

Animals↗
PubMed1983

Myocardial blood flow during exercise after gradual coronary occlusion in the dog.

Myocardial blood flow was studied with radioactive microspheres in 14 dogs 1 mo after placement of an Ameroid constrictor on either the left circumflex or the left anterior descending coronary artery to result in total coronary occlusion without myocardial infarction, as well as in 7 normal control dogs. Measurements were performed during quiet resting conditions and during two levels of treadmill exercise to achieve heart rates of approximately 180 (light exercise) and 230 beats/min (heavy exercise). During resting conditions myocardial blood flow in the collateral-dependent area was normal in all dogs. Three different patterns of response occurred during treadmill exercise in the animals with coronary occlusion. In five dogs, both the volume and transmural distribution of myocardial blood flow behaved similarly to the normal dogs at both exercise levels. In five dogs, blood flow behaved normally during light exercise, but during heavy exercise a transmural redistribution of perfusion occurred in the collateralized area to result in subendocardial underperfusion. Finally, in four dogs even light exercise resulted in subendocardial underperfusion in the collateral-dependent area, whereas further increasing the exercise load resulted in an actual decrease of subendocardial blood flow below the resting level. These data demonstrated that although resting myocardial blood flow was normal in the collateral-dependent area 1 mo after Ameroid implantation, a markedly heterogeneous response occurred during exercise, ranging from a completely normal response to a severe degree of exercise-induced subendocardial underperfusion.

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