ABSTRACT
It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 +/- 1 (mean +/- SEM) %, significantly lower than those in the untreated group and the eccentric dosing group (114 +/- 2%, 114 +/- 2%) (p < 0.01, respectively). In conclusion, eccentric dosing of nitrates inhibited the appearance of nitrate tolerance without reducing vascular response.
Subject(s)
Coronary Circulation/drug effects , Myocardial Ischemia/drug therapy , Nitroglycerin/administration & dosage , Vasodilator Agents/administration & dosage , Administration, Cutaneous , Administration, Oral , Administration, Sublingual , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aorta/physiology , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Cardiac Catheterization , Drug Tolerance , Female , Heart Rate/drug effects , Humans , Hypertension/drug therapy , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Ultrasonography, Doppler , Ultrasonography, Interventional , Vascular Resistance/drug effects , Vasodilation/drug effectsABSTRACT
This study was performed to investigate the risk of cardiac events by eccentric or continuous dosing of nitrates in patients with healed myocardial infarction. A total of 573 patients with healed myocardial infarction were assigned to one of two groups: a nitrate-treatment (n =239) and a nontreatment (n =334) group. The nitrate-treatment group was further subdivided into a group receiving eccentric dosing of nitrates (n =153) and a group receiving continuous dosing of nitrates (n =86). The mean observation period was 11.2+/-8.2 months. The cardiac events investigated were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, sudden death, worsening angina and rebound angina. Baseline characteristics were also compared among the three groups to determine any effects on outcome. Among the patients receiving eccentric or continuous dosing of nitrates, the rates of cardiac events were 12.7/1,000 person.year and 67.4/1,000 person.year, respectively, whereas the rate was 19.7/1,000 person.year in the nontreated patients. The incidence of cardiac events was significantly greater in patients receiving continuous dosing of nitrates than in the nontreated patients (p <0.05). Continuous dosing of nitrates thus increases cardiac events, and while eccentric dosing of nitrates does not increase them, it is also not effective at preventing them in patients with healed myocardial infarction.
Subject(s)
Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Nitroglycerin/administration & dosage , Vasodilator Agents/administration & dosage , Aged , Angina Pectoris/drug therapy , Angina Pectoris/mortality , Female , Heart Failure/drug therapy , Heart Failure/mortality , Humans , Incidence , Male , Middle Aged , Myocardium/pathology , Recurrence , Risk Factors , Survival Rate , Wound HealingABSTRACT
The effects on intimal hyperplasia of tissue plasminogen activator (tPA) and heparin following vascular injury were investigated. A common iliac artery in 34 hereditary hypercholesterolemic rabbits was injured by three successive 60-second balloon inflations to a pressure of 6 atm. Thereafter, two groups were continuously infused with tPA for 7 days at rates of 2 mg/kg per 24 hours (tPA-H) or 0.6 mg/kg per 24 hours (tPA-L), and two groups received intraarterial infusions of 750 U/kg (heparin-H) or 150 U/kg (heparin-L) heparin, followed by 625 U/kg or 125 U/kg subcutaneously twice daily for the same period, respectively. Twenty-eight days after injury, the intimal areas of the tPA-H (0.07 +/- 0.13 mm2), tPA-L (0.11 +/- 0.08 mm2), heparin-H (0.17 +/- 0.08 mm2), and heparin-L (0.28 +/- 0.27 mm2) groups were all significantly (P < 0.01) smaller than the controls (0.57 +/- 0.23 mm2), as were the intimal/medial cross-sectional area ratios (0.10 +/- 0.14, 0.21 +/- 0.20, 0.28 +/- 0.10, and 0.50 +/- 0.54 vs 1.13 +/- 0.74, respectively). Thus, attenuation of platelet aggregation by tPA or heparin inhibited medial smooth muscle cell proliferation and intimal hyperplasia in balloon injured arteries.
