Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning

Rinaldi, Christopher Aldo; Linka, André; Masani, Navroz; Avery, Philip; Jones, Elizabeth V.; Saunders, Helen; Hall, Roger

doi:10.1161/01.cir.98.8.749

“…The shortening fraction for all 12 segments (SFmean) and in the segments that developed the worst impairment after stress (SFworst) was calculated. Left ventricular volumes at end diastole and end systole were calculated using the biplane disk method, and global ejection fraction was derived as previously described 24. The coefficient of repeatability for this method was 2.6% as assessed by the method of Bland and Altman 25.…”

Section: Methodsmentioning

confidence: 99%

Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia

Barnes

¹

2000

Heart

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Objective-To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. Design-A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. Subjects-10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. Interventions-Treadmill exercise and dobutamine stress were performed on diVerent days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. Results-Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no diVerence in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), −5.6 (1.5)%, p < 0.05; and −6.1 (2.2)%, p < 0.01), and at 30 and 45 minutes after dobutamine (−10.8 (1.8)% and −5.5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst aVected segment 15 and 30 minutes after exercise (−27.9 (7.2)% and −28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (−32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). Conclusions-In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease. (Heart 2000;83:283-289)

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“…Most patients pretreated with nitrates demonstrated stunning at 24 hours after the angioplasty, whereas only 8% pretreated with nisoldipine showed stunning at 15 minutes after balloon deflation, and all had recovery of left ventricular function by 1 day after reperfusion. Rinaldi et al 15 also studied the effect of calcium channel blockade in patients undergoing exercise stress echocardiograms by comparing the effect of isosorbide mononitrate or amlodipine on postexercise wall motion abnormalities. As expected, shortening fraction was better preserved in patients on amlodipine than in those on nitrates.…”

mentioning

confidence: 99%

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

Kloner

¹

,

Jennings

²

2001

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Abstract-In experimental studies in the dog, total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult. The 15 minutes of ischemia, however, induce numerous changes in the myocardium, including certain monuments to the brief episode of ischemia that may persist for days. One of these monuments is stunned myocardium, which represents "prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion." The mechanism of stunning involves generation of oxygen radicals as well as alteration in calcium homeostasis and possibly alteration in contractile protein structure. Stunning has been observed in several clinical scenarios, including after percutaneous transluminal coronary angioplasty, unstable angina, stressinduced ischemia, after thrombolysis, and after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel blockers have been shown to enhance function of stunned myocardium in experimental studies, and in a few clinical studies, calcium channel blockers have been shown to ameliorate stunning. Although brief periods of ischemia can contribute to prolonged left ventricular dysfunction and even heart failure, they paradoxically play a cardioprotective role. Episodes of ischemia as short as 5 minutes, followed by reperfusion, protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis that results from the test episode of ischemia. This phenomenon, called ischemic preconditioning, has been observed in virtually every species in which it has been studied and is a powerful cardioprotective effect. The mechanism of ischemic preconditioning involves both triggers and mediators and involves complex second messenger pathways that appear to involve such components as adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, as well as others, including a paradoxical protective role of oxygen radicals. Both an early and a late phase of preconditioning have been described, and the mechanisms underlying their induction are under investigation. That preconditioning may occur in humans is suggested by the observations that repetitive balloon inflations in the coronary artery are associated with progressively less chest pain, ST-segment elevation, lactate production, the protective effects of preinfarction angina, the anginal "warm-up phenomenon," and studies performed on human cardiac biopsies that show metabolic properties suggesting preconditioning. Development of pharmacological agents that stimulate second messenger pathways thought to be involved in preconditioning, but without causing ischemia, could result in novel approaches to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a negative effect on the heart: stunning; and on the other hand, they have a protective effect: preconditioning. The future challenge is how to minimize the stunning phenomenon and maximize the preconditioni...

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“…Left ventricular volumes at end diastole and end systole were calculated using the biplane disk method, and global ejection fraction was derived as previously described. 24 The coefficient of repeatability for this method was 2.6% as assessed by the method of Bland and Altman. 25 The isovolumic relaxation period was used as an index of diastolic function.…”

Section: Echocardiographic Analysismentioning

confidence: 87%

Abnormal ventricular conduction following dothiepin overdose simulating acute myocardial infarction

Steeds¹

2000

Heart

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Objective-To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. Design-A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. Subjects-10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. Interventions-Treadmill exercise and dobutamine stress were performed on diVerent days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. Results-Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no diVerence in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), −5.6 (1.5)%, p < 0.05; and −6.1 (2.2)%, p < 0.01), and at 30 and 45 minutes after dobutamine (−10.8 (1.8)% and −5.5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst aVected segment 15 and 30 minutes after exercise (−27.9 (7.2)% and −28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (−32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). Conclusions-In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease. (Heart 2000;83:283-289)

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Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning

Cited by 36 publications

References 41 publications

Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia

Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

Abnormal ventricular conduction following dothiepin overdose simulating acute myocardial infarction

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