Increase In Pressure-rate Product Research Articles

Amlodipine in Residual Stable Exertional Angina Pectoris after Coronary Artery Bypass Surgery

Because of the long half-life (35 to 50 hours) of amlodipine, a calcium antagonist belonging to the dihydropyridine group, once-daily administration has been proposed. The aim of this study was to compare the effects of amlodipine and placebo on symptoms and exercise tolerance in patients with residual exertional angina after myocardial revascularisation. 16 patients (13 males, 3 females; mean age 61.9 ± 7.3 years) with chronic stable angina despite a previous myocardial revascularisation (more than 3 attacks per week after at least 3 months of pharmacological treatment) were enrolled. All patients had reproducible angina and >1mm horizontal or down-sloping ST-segment depression during two consecutive maximal exercise tests at the end of 2 weeks of a single-blind placebo period. A double-blind crossover study followed, in which 2 weeks on placebo were alternated with 2 weeks on amlodipine 10mg/day. An exercise cycloergometric test was performed 24 hours after the end of each treatment period. Concomitant antianginal treatment, with the exception of nitroglycerin, was not allowed. After administration of amlodipine, patients showed a significant increase in pressurerate product at ischaemic threshold (238 ± 27 vs 212 ± 29mm Hg • beats/min • 10−2; p<0.01) and an increase at peak exercise in ischaemic threshold (446 ± 84 vs 324 ± 96 sec; p<0.01), anginal threshold (469 ± 87 vs 394 ± 93 sec; p<0.01) and total exercise duration (515 ± 82 vs 398 ± 86 sec; p<0.01). Amlodipine also significantly increased total work to ischaemic threshold (2710 ± 908 vs 1590 ±752 kpm; p<0.01), angina (2930 ± 970 vs 2197 ± 912 kpm; p<0.01) and peak exercise (3223 ± 950 vs 2247 ±912 kpm; p<0.01). In conclusion, in these patients once-daily administration of amlodipine significantly increased the total exercise time and ischaemic and anginal thresholds, even 24 hours after the end of treatment, showing a prolonged anti-ischaemic protective effect.

Regulation of Cardiac Energy Turnover by Coronary Flow: a 31P-NMR Study

The response of cytosolic phosphates ([ATP], [PCr], [Pi] and [ADP]) in rat hearts retrogradely perfused with different oxidizable substrates to increased workload induced by elevated coronary flow (CF) or by addition of inotropic agents has been investigated. Hearts were perfused with glucose (11 mM), pyruvate (5 mM), lactate (3 mM) or a combination of glucose (5.5 mM) and acetate (5 mM), octanoate (0.1 mM) or β-hydroxybutyrate (5 mM). The initial [ATP]/[ADP] ratio was highest in pyruvate and lactate perfused hearts. Increasing the coronary flow 1.7-fold (from c. 56 to 96 ml/min × g dry wt) resulted in an increase in pressure-rate product (PRP) by 36-52% without significant changes in cytosolic phosphates. Dichloroacetate (1 mM), ruthenium red (2.5 μg/ml), or pre-treatment with theophylline (1 mM, 30 min) had no effect either functional or metabolic response to elevated CF in glucose-perfused hearts. Isoproterenol (Iso, 0.1 μM) infusion at maximal coronary flows lead to further elevation of PRP value by 36-88% and the ratio of the maximal rate of relaxation of LV developed pressure ((-d P/d t) m/LVDP) increased two-fold. Simultaneously, [PCr] decreased by 18-30%, [Pi] increased two fold and ADP increased by 20-90% resulting in reduction of [ATP]/[ADP] by half and ATP affinity (A(ATP = - ΔG(ATP)) by 2.4-3.8 kJ/mol. In hearts perfused with acetate, octanoate and hydroxybutyrate in the presence of glucose, Iso addition resulted in intracellular pH decrease by 0.03-0.07 U and increase in lactate extrusion 1.5-2 times. In hearts perfused with glucose alone, decrease in PRP induced by perfusate Ca 2+ reduction was associated with increase in PCr and decrease in Pi levels. These data show that coordinated regulation of energy supply and demand exerted by coronary flow/perfusion pressure does not depend on the availability of reducing equivalents but is rather controlled by oxygen supply and stretch-activated factors.

Effects of catecholamine stimulation on myocardial hibernation

We have recently shown that low-flow (10%) ischemia in the isolated piglet heart causes an abrupt fall in mechanical function and metabolic activity (acute hibernation), with nearly complete preservation of high-energy phosphates and glycogen after 2 hours of ischemia. We attempted to determine if norepinephrine, as occurs in vivo, would modify the hibernation process. Piglet hearts were perfused at 37° C with red blood cell-enhanced Krebs-Henseleit solution. Performance of the left ventricle was assessed isovolumetrically. With control coronary flow, norepinephrine (40 ng/ml) caused a ≈50% increase in pressure-rate product and the rate of change of pressure. When coronary flow was reduced to 10%, these measures fell to levels indentical to those of ischemic hearts not exposed to norepinephrine. Changes in myocardial O 2 metabolism paralleled mechanical function. Lactate release was quantitatively similar in both groups. However, myocardial adenosine triphosphate was reduced from 29 ± 1 to 13 ± 2 μmol/gm and glycogen from 300 ± 46 to 77 ± 15 μmol/gm by the presence of norepinephrine. Left ventricular compliance was reduced to 51 ± 5%, compared with 87 ± 8% in the group without norepinephrine ( p < 0.001). In the norepinephrine group, correlation between left ventricular stiffness and adenosine triphosphate was poor ( r = −0.32). Thus hibernating myocardium does not manifest progressive deterioration in the presence of high concentrations of norepinephrine. Diastolic function is less well preserved, however.

Non-invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion

Electrocardiographic changes after dipyridamole infusion (0.568 mg/kg/4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non-MI group), 14 with anterior infarction (ANT-MI) and eight with inferior infarction (INF-MI). Eighty-seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.