Hemodynamic and electrophysiologic effects of amlodipine, a new calcium channel blocker.

The effects of amlodipine (300 micrograms/kg administered intravenously), a new, long-acting, dihydropyridine class, calcium channel blocking drug, were studied in atrially paced (120 beats/min), autonomically blocked dogs. Hemodynamic and electrophysiologic parameters were measured before and up to 3 hours after amlodipine. Coronary blood flow was significantly increased 10 and 30 minutes after drug administration, whereas cardiac output and mean arterial pressure were unaffected. Coronary vascular resistance was decreased but total systemic vascular resistance did not change. Atrioventricular (AV) nodal conduction was slightly prolonged, as reflected by increases in atrial-His bundle and AV conduction times and PR interval, 30 minutes after administration. All parameters returned toward their control values within 3 hours after drug administration. Comparison of coronary vascular resistance and AV conduction changes with those previously reported for other calcium channel blocking drugs where autonomic blockade existed suggests that at equivalent levels of coronary vasodilation, amlodipine's effects more closely resemble the effects of diltiazem or verapamil than other dihydropyridines.

Protection of regional mechanics and mitochondrial oxidative phosphorylation by amlodipine in transiently ischemic myocardium.

The effects of amlodipine (0.3 mg/kg administered intravenously, n = 5) and placebo (n = 5) on recovery of myocardial function and respiration of isolated mitochondria were examined in "stunned" myocardium of normotensive pentobarbital-anesthetized dogs. Measures of myocardial wall motion, using sonomicrometers, and tissue blood flow, by radioactive microspheres, were obtained at baseline, 15 minutes after administration of amlodipine or placebo, after 10 minutes of left circumflex artery ligation and at 60 minutes of reperfusion. Mean aortic pressure decreased from 115 +/- 6 to 101 +/- 5 mm Hg after administration of amlodipine and remained decreased throughout the experiment. Heart rate was not significantly affected at any time. Both groups showed similar degrees of ischemia: elevation of ST segment to 4.7 +/- 1.4 vs 6.2 +/- 1.9 mV; reduction of ischemic zone shortening fraction to 0.6 +/- 1.9 vs -3.4 +/- 2.7%; and reduction of epicardial and endocardial blood flows (epicardial = 40 +/- 13 vs 43 +/- 13 ml/100 g/min; endocardial = 7 +/- 4 vs 13 +/- 6 ml/100 g/min [values for amlodipine vs placebo]). Mitochondrial state 3 rate of respiration and respiratory control index indicative of rate of adenosine triphosphate synthesis and membrane integrity in myocardial samples taken after 10 minutes of ischemia were significantly reduced in the placebo but not in the amlodipine group. Myocardial function showed significantly greater improvement in amlodipine vs placebo at 60 minutes of reperfusion as indicated by shortening fraction (17.7 +/- -1.4 vs 5.8 +/- -3.5%, amlodipine vs placebo), which may have been related to increased myocardial blood flow and decreased blood pressure during reperfusion. Thus, amlodipine pretreatment prevented mitochondrial dysfunction during ischemia and accelerated recovery of both myocardial mechanical function and blood flow when compared with placebo.

Development of a method to determine autonomic nervous system function in the rat.

A noninvasive method to evaluate autonomic nervous system (ANS) function in animals is needed for studies of diabetic autonomic neuropathy. These studies modified the RR-variation test, used to test diabetic ANS function in humans, and applied it to rats. Permanent wire electrodes were implanted in the chest wall of a rat. ECG complexes were obtained by connecting the electrodes to leads going to an impedence pneumograph and high gain coupler. This information was then converted into square waves by a trigger unit and recorded on magnetic tape for subsequent analysis by computer. Recordings were at least 60 seconds long, of which 30 seconds was used for analysis. In order to establish autonomic influence, RR-variation was measured before and after application of pharmacologic agents. Directly decreasing parasympathetic tone with atropine (20 mg/kg, n = 6) increased heart rate (P less than 0.001) and decreased RR-variation (P less than 0.05). Directly decreasing beta adrenergic tone with propranolol (10 mg/kg, n = 7) decreased heart rate (P less than 0.01) but had no effect on RR-variation (NS). Stimulation of the beta adrenergic receptors (isoproterenol, 0.1 mg/kg, n = 5) increased heart rate (P less than 0.01) but decreased RR-variation (P less than 0.01). Increasing parasympathetic tone reflexly with alpha-1 adrenergic receptor stimulation (phenylephrine, 1 mg/kg, n = 7) decreased heart rate (P less than 0.05) and increased RR-variation (P less than 0.025). The responses to phenylephrine could be blocked by parasympathetic blockade. Phentolamine (0.1 mg/kg, n = 7) caused an increase in heart rate (P less than 0.001) and a decrease in RR-variation (P less than 0.01). The responses to phentolamine could be blocked by beta adrenergic receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost incentives for peripheral angioplasty.

Hospital costs and length of stay for 86 patients with peripheral vascular disease treated by bypass or percutaneous transluminal angioplasty (PTA) were assessed. The length of stay averaged 4-4.5 times longer, and the total hospital charge was 3-3.7 times greater, for bypass than for PTA. These charges are discussed in relation to current diagnosis-related groups (DRGs) and the allowed reimbursement from the Federal Prospective Payment System. In appropriately selected patients with peripheral vascular disease, PTA should be the treatment of choice from both medical and financial points of view.

Documentation of care and prospective payment. One hospital's experience.

Hospitals are now being reimbursed by Diagnosis Related Group (DRG) for Medicare patients. The Johns Hopkins Hospital has worked successfully under this system for the past 5 years, with cost increases being maintained well below the national average. Allowable revenue varies considerably by diagnosis depending on such factors as secondary diagnoses, procedure, and patient age. Failure to document accurately may result in substantial loss of hospital income. More worrisome is the use of data by outside agencies to evaluate quality of care. Recent reports of mortality rates for surgery in Maryland hospitals and of permanent pacemaker use are illustrative. Conclusions were inaccurate because of inadequate documentation of diagnoses and procedures by physicians and inaccurate coding by quality assurance coordinators. Surgeons need to be aware that in the prospective payment era, accurate and complete documentation is essential and that their data are likely to be used for purposes other than monitoring fiscal performance.