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Clinical studies with transdermal nitroglycerin.

Abstract

The short- and long-term effects of various Nitro-Dur formulations on performance and hemodynamics were studied in 15 men with stable angina pectoris who also had a positive treadmill exercise test. A treadmill exercise score (TES) was used that quantified the "ischemic" ST segment response to exercise. The score incorporated information that reflected the rapidity of evolution of ST segment depression during exercise and the time required for it to resolve after cessation of exercise. In early tests (n = 10) Nitro-Dur improved both the TES (by 31%: p less than 0.0001) and the time required for 1 mm ST segment depression (by 33%: p less than 0.0001). At all dosage levels, Nitro-Dur also decreased resting systolic blood pressure and increased resting heart rate. No dose-response patterns emerged. Changes in TES and time to ST segment depression were greater with sublingual nitroglycerin than they were with Nitro-Dur. In tests conducted after prolonged dosage (n = 5), the effects of Nitro-Dur on blood pressure and heart rate became attenuated at weeks 2 and 4, although cardiac responsiveness was preserved, as reflected in the increased time required before the occurrence of 1 mm ST segment depression. The latter effect was also observed with sublingual nitroglycerin. The clinical relevance of these data to the design of individual patient therapy is discussed.

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BibTeXRIS

M Hollenberg, M Go. 1984. Clinical studies with transdermal nitroglycerin.. https://doi.org/10.1016/0002-8703(84)90579-9

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Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.

OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

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