L. Chiariello

Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker.

BackgroundBrief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preconditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (KATP) channels. The role played by KATP channels in preconditioning in humans remains unknown. The aim of this study was to establish whether glibenclamide, a selective KATP channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations. Methods and ResultsTwenty consecutive patients undergoing one-vessel coronary angioplasty were randomized to receive 10 mg oral glibenclamide or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8 mL/min) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusion, both patient groups underwent coronary angioplasty. The mean values (± 1 SD) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide-treated patients, the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation (23± 13 versus 20±8 mm, P=NS), and the severity of cardiac pain was greater (55±21 versus 43±23 mm on a scale of 0 to 100, P<.05). Conversely, in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation (9±5 versus 23±13 mm, P<.001), as was the severity of cardiac pain (15±15 versus 42±19 mm, P<.01). Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline (53±9 versus 102±10 mg/100 mL, P<.001) in the glibenclamide group; however, before coronary angioplasty, blood glucose levels increased to 95±19 mg/100 mL, a value similar to that found in placebo group (96±11 mg/100 mL, P=NS). ConclusionsIn humans, ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by KATP channels.

Ischemic Preconditioning in Humans Models, Mediators, and Clinical Relevance

Ischemic preconditioning, a powerful form of endogenous protection against myocardial infarction, has been demonstrated in several animal species and, recently, in isolated human cardiomyocytes. For both logistic and ethical reasons, no clinical study can meet the strict conditions of experimental studies on preconditioning with infarct size as the end-point. Nevertheless, the demonstration of adaptation to ischemia observed during in vitro studies on human atrial trabeculae, in patients in the setting of coronary bypass surgery, and in the setting of coronary angioplasty in the absence of collateral vessel recruitment strongly suggests that ischemic preconditioning occurs in humans. This notion is further supported by the observation that in these human models, the adaptation to ischemia is influenced by drugs acting on K(ATP) channels and on purinergic and alpha-adrenergic receptors, similar to what is observed in accepted experimental models of ischemic preconditioning. This important form of myocardial endogenous protection may also play a role in the warm-up phenomenon and in mediating the beneficial effects of preinfarction angina. The demonstration of ischemic preconditioning in humans and the identification of some of its mediators suggests that in patients at high risk for myocardial infarction, drugs known to block this endogenous form of protection should be used with caution, whereas drugs known to elicit preconditioning might have a relevant therapeutic role.

Bamiphylline improves exercise-induced myocardial ischemia through a novel mechanism of action.

BackgroundIn patients with stable angina pectoris aminophylline, a nonselective antagonist of adenosine receptors, markedly improves exercise capacity. To establish the role played by A, adenosine receptors in the anti-ischemic action of aminophylline, the effects of bamiphylline, a selective A, antagonist, on exercise-induced ischemia were investigated in patients with stable angina pectoris. Methods and ResultsIn a single-blind, placebo-controlled, randomized cross-over trial in 18 patients, oral administration of 1200 mg bamiphylline increased both the time to 1-mm ST segment depression (from 524 ± +177 to 664 ± 192 seconds, p<.01) and the rate-pressure product at 1-mm ST segment depression (from 159 ± 31 to 190 ± 34 beats per minute per mm Hg/104 (P<.001). End-diastolic and end-systolic left ventricular volumes, left ventricular ejection fraction, and systolic septal and posterior wall thickening investigated by two-dimensional echocardiography in 12 of the 18 patients were not affected by oral administration of bamiphylline (124 ± 22 versus 125 ± 20 mL, P=NS; 49 ± f12 versus 50 ± +13 mL, P=NS; 60 ± 8% versus 58 ± 7%, P=NS; 35 ± 6% versus 36 ± 7%, P=NS; 32 ± 6% versus 33 ± 6%, P=NS, respectively). In 7 of the 18 patients, the intravenous infusion of bamiphylline (5 mg/kg in 15 minutes) during cardiac catheterization did not produce any significant change of heart rate (76 ± 10 versus 75 ± 13 beats per minute, P=NS), mean right atrial pressure (3.8 ± +1.7 versus 3.7 ± 1.7 mm Hg, P=NS), mean aortic pressure (102 ± +12 versus 99 ± +10 mm Hg, P=NS), or left ventricular end-diastolic pressure (14 ± 3 versus 14 ± 4 mm Hg, P=NS) compared with baseline. Furthermore, after intravenous infusion of bamiphylline, the diameter of seven proximal and distal normal segments and of seven stenotic segments were similar to those measured at baseline (3.1 ± 0.5 versus 3.1 ± 0.5 mm, P=NS; 1.6 ± 0.2 versus 1.7 ± 0.2 mm, P=NS; 1.6 ± 0.5 versus 1.6 ± 0.5 mm, P=NS, respectively). ConclusionIn patients with stable angina pectoris, oral administration of bamiphylline improves exercise capacity. Its anti-ischemic action does not appear to be mediated by systemic hemodynamic effects or by stenosis dilation. Therefore, the improvement of myocardial ischemia caused by bamiphylline is probably due to redistribution of coronary blood flow toward the underperfused subendocardium. This novel anti-ischemic action would appear to be mediated by antagonism of A1 receptors.

Determinants of myocardial ischemia during percutaneous transluminal coronary angioplasty in patients with significant narrowing of a single coronary artery and stable or unstable angina pectoris

Previous studies have assessed the determinants of collateral vessel recruitment during coronary occlusion in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). However, the determinants of severity of myocardial ischemia after sudden coronary occlusion do not necessarily coincide with those responsible for collateral vessel recruitment. The aim of this study was to assess the determinants of severity of myocardial ischemia during balloon inflation by recording surface and intra-coronary electrocardiograms (ECGs). In 62 consecutive patients with 1-vessel disease and without previous myocardial infarction undergoing successful PTCA for stable (n = 33) or unstable (n = 29) angina pectoris, the summation of the absolute values of ST-segment shifts from baseline on the intracoronary and surface ECG at the end of the first 2-minute inflation was obtained as an index of the severity of myocardial ischemia. Stenosis severity before PTCA was measured using computerized coronary angiography, while the grade of collateral filling was scored according to Rentrops classification. The mean (+/- 1 SD) ST-segment shift at the end of balloon inflation was less in patients with than without collateral vessels (12 +/- 10 vs 23 +/- 15 mm, p < 0.05). Despite a similar prevalence of collateral vessels (34% vs 24%, p = NS), the mean ST-segment shift was also less in patients with unstable than stable angina (15 +/- 9 vs 24 +/- 17 mm, p < 0.05). However, the mean ST-segment shift was not associated with the severity of coronary stenosis before PTCA (r = 0.0004, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Early coronary artery bypass graft thrombosis in a patient with protein S deficiency

A 59-year-old white man underwent multiple coronary artery bypass grafts (CABGs) on an emergency basis for severe stenosis of the left main, and occlusion of the right coronary, artery. One month after operation recurrence of angina prompted a new diagnostic evaluation. Occlusion of the grafts was detected at angiography. Accurate hematological screening before reoperation showed decreased levels of protein S. One year after his second operation, the patient is asymptomatic on oral anticoagulant therapy. Tallium-201 scintigraphy shows normal myocardial perfusion.

The Valsalva graft in aortic valve repair and replacement.

Presentation of the use of the new Valsalva graft that incorporates sinuses of Valsalva: its use is mostly recommended for the reimplantation type of valve sparing procedure where it combines the advantages of proper anatomical reconstruction with those of annular stabilization. Its advantages when used in the remodeling technique or in a classical Bentall procedure are also shown. The problem of graft sizing and of proper geometrical reconstruction of the aortic root are addressed.