Effects of beta-blockade on regional myocardial flow and function during exercise

Matsuzaki, Masunori; Patritti, José Pedro; Tajimi, Tsukasa; Miller, Maria Elisa Peinado; Kemper, W S; Ross, Jennifer Gunberg

doi:10.1152/ajpheart.1984.247.1.h52

Cited by 49 publications

(41 citation statements)

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“…27 We have previously reported a high degree of reproducibility in sequential runs performed 3 hr apart in this animal preparation without intervention, with very similar responses of regional blood flow, hemodynamics, and regional wall thickening in both ischemic and normal zones.27…”

Section: 8-adrenergic Blockade Is Effective In Im-mentioning

confidence: 73%

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

Matsuzaki¹,

Guth²,

Tajimi³

et al. 1985

Circulation

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The effect of combination therapy with diltiazem and atenolol on the regional myocardial blood flow-function relationship was studied in eight conscious dogs with chronic coronary artery stenosis. An ameroid constrictor and hydraulic occluder were placed around the left circumflex coronary artery, sonomicrometers were implanted for measuring wall thickness in control and ischemic regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery, resting regional myocardial function and blood flow were normal, but treadmill exercise induced severe regional myocardial dysfunction in the posterior wall (wall thickening during systole reduced from 25.5% to 2.7%, a 90% reduction). Subendocardial blood flow decreased by 68% from the control standing value, while subepicardial flow increased. An identical exercise bout was performed 3 hr after administration of atenolol (1.0 mg/kg orally) and 15 min after administration of diltiazem (0.3 mg/kg iv). Heart rate during running was significantly lower as were left ventricular peak systolic pressure, end-diastolic pressure, and peak dP/dt. Wall thickening in the control region was not augmented during exercise after atenolol and diltiazem. There was less dysfuncion in the ischemic region (35% reduction) and the improved performance was accompanied by a substantial increase in subendocardial perfusion (0.31 + 0.14 vs 0.61 + 0.30 ml/min/g, a 36% reduction from rest). Epicardial flow was unchanged, and the endocardial/epicardial ratio increased (0.27 + 0.13 vs 0.62 + 0.29). Recovery time for regional wall thickening also improved. The beneficial effects of the combination of atenolol and diltiazem in a preparation of single-vessel chronic coronary stenosis were shown to be significantly greater than those of either drug alone. Circulation 72, No. 1, 233-243, 1985. ,8-ADRENERGIC BLOCKADE is effective in improving exercise tolerance in patients with angina pectoris but sometimes optimum results are not achieved when the drugs are used alone.'`A second drug is therefore sometimes added to therapy, such as a longacting nitrate,4 a calcium blocker,5 ' or occasionally digitalis.8 Calcium channel-blocking drugs, which inhibit the influx of calcium ions during cell depolarization in both smooth and cardiac muscle, are highly effective in the therapy of vasospastic myocardial ischemia and stable angina pectoris.

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Section: 8-adrenergic Blockade Is Effective In Im-mentioning

confidence: 73%

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

Matsuzaki¹,

Guth²,

Tajimi³

et al. 1985

Circulation

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“…Similar results have been shown with ,B-adrenergic antagonists.6 9 However, in a model of exercise-induced ischemia when the bradycardia produced by atenolol was prevented by pacing, regional myocardial blood flow An inverse relation between subendocardial perfusion and heart rate has been shown in exercising dogs with restricted coronary inflowl"32 and during cardiac pacing in a normally perfused bed with maximal vasodilation,2 and several other studies have shown beneficial effects of P-blocking agents during different types of ischemia. [6][7][8][9][10]12 Previous studies on the mechanisms by which bradycardic drugs decrease regional ischemia due to coronary artery stenosis have shown increased subendocardial to subepicardial myocardial blood flow ratios during P-blockade or increased subendocardial blood flow with unchanged subepicardial flow after N-dimethyl propranolol (which has no ,B-blocking properties). "1 Other studies with more severe ischemia showed increased subendocardial blood flow without significant change in subepicardial flow after several l-blocking agents were administered and also showed increased distal perfusion pressure and a marked reduction in calculated resistance of a coronary artery stenosis.…”

Section: Potential Mechanisms Of Improved Contractionmentioning

confidence: 99%

“…[8][9][10][11][12] However, a number of confounding variables in the studies in resting animals have limited our understanding of the effects of the bradycardia per se on the relations between regional blood flow (as an index of oxygen supply) and regional contraction (as an index of oxygen demand). Thus, changes in coronary stenosis resistance,10 unknown contributions of collateral blood flow,8 and possible unopposed a-adrenergic constrictor effects after ,Badrenergic receptor blockade13 can affect total regional blood flow and its distribution.…”

mentioning

confidence: 99%

Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine.

et al. 1989

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In anesthetized swine, the left anterior descending coronary artery was cannulated and perfused at constant blood flow levels during two grades of ischemia. In one group (n = 10), moderate ischemia reduced percent systolic wall thickening (by sonomicrometry) from 25+±7% to 6±2%, whereas in the other group (n =7), severe ischemia reduced percent wall thickening from 24+6% to -0.5+4%. Heart rate was paced in both groups at 91 beats/min. After reperfusion and complete return to control conditions, administration of the bradycardic agent UL-FS 49 (0.37 mg/kg i.v.) decreased the heart rate to 55±5 beats/min. During subsequent ischemia at the same coronary inflow as before bradycardia, percent wall thickening in the ischemic zone during moderate ischemia was increased from 6+2% to 25 ±6% (p<0.01) (not significantly different from control without ischemia), and during severe ischemia, percent wall thickening increased from -0.5±4% to 13 ±7% (p <0.01). During moderate ischemia, bradycardia caused an increase in the subendocardial blood flow from 0.24+±0.60 to 0.42+±0.17 (ml/min)/g (p<0.009) and during severe ischemia, bradycardia caused an increase from 0.14±0.08 to 0.2+0.1 (ml/min)/g (p<0.001). At each level of ischemia, a more marked improvement occurred in subendocardial blood flow per beat ([(ml/min)/g]/heart rate). The relation between myocardial blood flow and wall function at a heart rate of 55 beats/min (n = 14) was plotted and compared with that studied at a heart rate of 122 beats/min in another group of pigs (n = 14). The increase in subendocardial blood flow per minute during bradycardia was not sufflicient to explain the striking increase in function; thus, an independent relation (p<0.05) between blood flow per minute and contractile function (percent wall thickening) was found for each heart rate. In contrast, when myocardial blood flow was normalized for heart rate and expressed per beat, data from both heart rate groups could be described by a single relation. Thus, the subendocardial blood flow per beat predicted wall function independently of heart rate and accounted for changes in both oxygen supply and demand. (Circulation 1989;80:983-993) I ncreased heart rate aggravates myocardial ischemia,1-4 and pharmacologic reduction of heart rate by ,B-adrenergic blockade has been an important form of therapy in patients with coronary artery disease. Mechanisms involved in the

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“…Segment shortening 15 min after persistent stenosis runs was reduced compared with temporary stenosis runs (see Fig. 7), but not compared with preexercise control (Table III).…”

Section: Resultsmentioning

confidence: 87%

“…15 ,um in diameter, labeled with gamma-emitting nuclides (125i, 14Ce, 51Cr, 85Sr, 95Nb, "3Sn, and 4Sc). Before injection, the microspheres were agitated for at least 15 min in an ultrasonic bath.…”

Section: Introductionmentioning

confidence: 99%

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

Homans¹,

Sublett²,

Dai³

et al. 1986

J. Clin. Invest.

139

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To determine whether regional myocardial dysfunction occurring after exercise-induced ischemia 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 hypoperfusion was noted 1 min after exercise (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.

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Effects of beta-blockade on regional myocardial flow and function during exercise

Cited by 49 publications

References 0 publications

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine.

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

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