Persistence of subendocardial perfusion after subtotal coronary embolisation.

The effects of acute subtotal embolisation of small coronary arteries on regional coronary flow and vasodilator reserve were investigated in seven open chest dogs. Unlabelled plastic microspheres (26(2) micron in diameter) were injected as boluses of 200,000-400,000 microspheres into the circumflex artery. Embolisation was repeated until reactive hyperaemia was totally abolished, which occurred after the injection of 62,000(4000) microspheres per gram. Intracoronary adenosine was then infused for 20 min at 1.2 mg.min-1. Regional myocardial blood flow was measured by radioactive microspheres under control conditions, after coronary embolisation, and during adenosine infusion. Coronary blood flow (0.98(0.07) ml.min-1.g-1) was reduced to 0.66(0.08) ml.min-1.g-1 after embolisation (p less than 0.005) when reactive hyperaemia was practically abolished. Embolisation reduced epicardial flow from 0.93(0.08) to 0.40(0.09) ml.min-1.g-1 (p less than 0.001), whereas endocardial flow was unchanged (1.03(0.11) vs 0.92(0.14) ml.min-1.g-1; NS); as a consequence, the endocardial to epicardial flow ratio increased from the control value of 1.11(0.06) to 2.31(0.35) (p less than 0.005). Adenosine infusion increased coronary blood flow from 0.66(0.08) to 1.66(0.41) ml.min-1.g-1 (p less than 0.05). Endocardial blood flow increased more than epicardial blood flow, leading to a further increase in the endocardial to epicardial flow ratio (3.79(0.13); p less than 0.05). Thus it is concluded that (a) embolisation of small arteries abolishes the reactive hyperaemic response to transient coronary occlusion; (b) microembolisation predominantly reduces subepicardial perfusion; and (c) adenosine administration may increase total and regional flow after subtotal occlusion of coronary small arteries.

Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia: correlation with exercise electrocardiography.

BACKGROUND: Nisoldipine, a dihydropyridine calcium channel blocker with strong coronary dilatative action, is commonly used in the treatment of myocardial ischaemia; its beneficial effect on effort angina has been demonstrated by several previous reports. Infusion of dipyridamole in doses sufficient to provoke myocardial ischaemia in patients with significant coronary artery disease is used safely in imaging studies for diagnostic purposes. OBJECTIVE: To evaluate the potential effect of nisoldipine on dipyridamole-induced ischaemia and to compare the results with the effect of nisoldipine on exercise-induced ischaemia. METHOD: Twelve patients (10 men and two women, mean age 62 +/- 8 years) with significant coronary artery disease (at least 70% lumen reduction in at least one major coronary vessel) were selected for inclusion in the study. In accordance with the inclusion criteria, the patients exhibited an ischaemic diagnostic response to a multistage exercise electrocardiography stress test (> 0.15 mV ST segment depression compared with the resting electrocardiographic tracing) and to a dipyridamole-echocardiography test (transient left ventricular dyssynergy of contraction during infusion of dipyridamole up to 0.84 mg/kg over 10 min), after 3 days' cessation of antianginal treatment. After treatment with oral nisoldipine (10 mg twice daily) was introduced, the patients repeated the two tests, within 18 days of the first evaluation. RESULTS: The dipyridamole-echocardiography test was positive for ischaemia in 12 patients who were not receiving nisoldipine and in eight patients who were receiving the drug (100% and 67% respectively, P < 0.05). In the eight patients who gave positive dipyridamole-echocardiography tests both with and without treatment, dipyridamole time (time to onset of dyssynergy during the test) increased from 7.9 +/- 2.9 min to 10.2 +/- 3.1 min (P < 0.01). In these patients, no significant changes were observed, at ischaemia, in the severity and extent of induced dyssynergy, evaluated as wall motion score index (each of 16 left ventricular segments scored from 1 = normal to 4 = dyskinetic) after treatment (score variations from baseline to ischaemia: 0.20 +/- 0.11 without nisoldipine and 0.16 +/- 0.06 with nisoldipine; NS). Variations in dipyridamole time (arbitrarily considered to be 15 min in the negative dipyridamole-echocardiography test) were significantly correlated with variations in exercise time (duration of exercise to exhaustion or diagnostic positive response on the electrocardiogram): r = 0.75 (P < 0.01). No significant differences were recorded in rate-pressure product (beats/min x mmHg x 100) at peak ischaemia between patients who were or were not receiving nisoldipine, during either the exercise electrocardiography stress test (233 +/- 36 with nisoldipine and 244 +/- 39 without nisoldipine; NS) or the dipyridamole-echocardiography test (147 +/- 21 with nisoldipine and 133 +/- 30 without nisoldipine; NS). CONCLUSION: Nisoldipine treatment can protect from dipyridamole-induced ischaemia, being associated with a longer stress time, and completely preventing the development of ischaemia in some patients. The therapy-induced changes in ischaemic threshold during the dipyridamole-echocardiography test correlate with variations in exercise tolerance.

Elective response to propranolol or verapamil in ischemia on effort.

Twenty-four patients with effort angina and positive exercise stress test performed four control exercise stress tests, two tests while taking propranolol (240 mg/day) and two tests while taking verapamil (320 mg/day), in a randomized crossover sequence. For each test the following parameters were measured: time and rate-pressure product at ischemia; intercept and slope of the linear regression between rate-pressure product and minutes of exercise. Group analysis showed that both drugs improved time to ischemia significantly and to the same extent. However, eight patients responded preferentially to verapamil in contrast to 12 patients on propranolol. The remaining four patients responded equally to both drugs. In verapamil responders, verapamil increased time to ischemia by decreasing intercept and increasing rate-pressure product at ischemia. In these patients, propranolol did not increase time to ischemia because of a marked decrease in rate-pressure product at ischemia. In propranolol responders the significant increase in time to ischemia during propranolol was the result of a decrease in intercept and slope. The ineffectiveness of verapamil in these patients was related to a slight decrease in intercept without any increase in rate-pressure product at ischemia. The preferential response to one of the two drugs could not be predicted on the basis of clinical and angiographic features. In conclusion, in patients with effort angina, medical treatment should be personalized and based on a direct and objective verification of a drug's efficacy since different mechanisms can modulate exercise tolerance.

Individual variability in symptoms, ischemic threshold and cardiovascular efficiency during exercise testing in patients with effort angina.

This study assessed both group and individual variability of ECG exercise stress test in patients with effort angina. Forty-five untreated patients with typical effort angina, without evidence of spontaneous angina, with a positive exercise stress test (ST depression greater than 0.2 mV) and angiographically documented coronary artery disease were studied. Four multistage exercise stress tests were performed, two in the morning and two in the afternoon, on two consecutive days. Forty-four patients completed the protocol for a total of 176 exercise stress tests. For each exercise stress test the following parameters were analyzed: time to 0.15 mV ST segment depression (time to ischemia); rate-pressure product at ischemia (ischemic threshold); slope and intercept of the linear regression between rate-pressure product and time of exercise. Silent effort ischemia was largely prevalent: 21 patients (48%) experienced chest pain in all four tests, but only seven showed a consistent time relationship between pain and ECG changes. Symptomatic patients did not appear different from the asymptomatic ones in terms of clinical and angiographic data. When group data were analyzed for each parameter the four exercise stress tests appeared reproducible. In contrast, when individual variability of each parameter was computed as the percentage difference between range (maximum--minimum) and maximal value obtained in the series of four exercise stress tests, a large variability was detected. Variability of time to ischemia, was 27.2 +/- 17.4%. This resulted from a random combination of variability in ischemic threshold (19.1 +/- 9.2%), slope (28.4 +/- 12.8%) and intercept (22.7 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperkinetic ventricular arrhythmias in very elderly people with and without cardiac disease. Correlation with left ventricular echocardiographic parameters.

BACKGROUND: Morphological and functional changes induced by aging can hamper a clear distinction between pathological or paraphysiological phenomena in very old people. The incidence of hyperkinetic ventricular arrhythmias, for example, progressively increases in the elderly, even in the absence of overt cardiac disease. METHODS: One-hundred fifty-two clinically stable patients older than 80 years, submitted within 15 days to clinical evaluation, 24-hour continuous ambulatory ECG monitoring and echo Doppler examination, in the absence of antiarrhythmic treatment, were retrospectively selected in order to evaluate the incidence of ventricular arrhythmias, in patients with and without significant heart disease. The further aim of the study was to correlate the number of arrhythmias with left ventricular morphological and functional parameters, echocardiographically assessed. From the initial population, 80 patients (41 males, age 83 +/- 3 years) had significant heart disease (ischemic, hypertensive or valvular): Group I. Seventy-two patients (30 males, age 83 +/- 3 years) had no clinical or instrumental signs of heart disease: Group II. RESULTS: Considering echocardiographic data, Group I patients had a significantly higher left ventricular end-diastolic diameter (52 +/- 6 mm vs 47 +/- 4 mm, p < 0.01), lower ejection fraction (57 +/- 10% vs 64 +/- 6%, p < 0.01) and higher mass (275 +/- 84 g vs 208 +/- 46 g, p < 0.01), when compared with Group II. From ECG monitoring data, significant differences between the two groups were recorded in the incidence of premature ventricular beats per hour (79 +/- 163 vs 15 +/- 34, Group I vs Group II, p < 0.01) and presence of complex phenomena (couplets, triplets and runs: 51% vs 22%, p < 0.01). In old patients with documented cardiac disease a significant correlation was present between premature ventricular beats incidence and left ventricular end diastolic diameter (r = 0.39, p < 0.05) and left ventricular ejection fraction (r = 0.40, p < 0.05), while in patients without heart disease, no significant correlation was found between incidence of premature ventricular beats and echocardiographic morpho-functional parameters. CONCLUSIONS: In conclusion, hyperkinetic ventricular arrhythmias are globally frequent in old persons of very advanced age (more than 80 years), but, also in this subset, a significant distinction in terms of incidence and severity of arrhythmias is present between subjects with and without cardiac disease. A significant correlation between incidence of premature beats and non-invasive morpho-functional left ventricular parameters is present only for patients with overt heart disease.

Regional myocardial performance before, during and after coronary occlusion.

The effects of transient coronary occlusion upon segment length and intramyocardial pressure were studied in seven open-chest dogs. The subendocardial and subepicardial layers in the territory of the left anterior descending coronary artery were instrumented with pairs of ultrasonic crystals and miniature pressure probes. During coronary occlusion, systolic subendocardial pressure decreased from 194 +/- 11 to 141 +/- 12 mmHg (p 0.001) and systolic subepicardial pressure from 82 +/- 7 to 62 +/- 12(p 0.05). Systolic shortening was abolished in both layers. During reperfusion, systolic subendocardial pressure reached 242 +/- 22 mmHg (p 0.05) and systolic subepicardial pressure 100 +/- 10 mmHg (p 0.05). Early during reperfusion a transient overshooting was also observed in subendocardial and subepicardial systolic shortening. The observations of this study are consistent with the hypothesis that unrestricted reperfusion is associated with an overshooting in regional myocardial contractile performance.

Dipyridamole-echocardiography test as a clue for assessing the organic 'ceiling' of individual coronary reserve.

Twenty-four patients with a history of effort angina, a positive exercise stress test (EST) and coronary artery disease were enrolled in the study; 12 patients had a positive dipyridamole-echocardiography test (DET) and 12 had a negative DET. Each patient performed a total of 4 ESTs in the absence of therapy on two successive days; for each test the rate-pressure product (RPP), an established index of myocardial oxygen demand, was measured at the onset of ischaemia (ST depression greater than 0.15 mV) or at the peak of maximal exercise (if a repeated EST was negative). Taking into account the lowest of the 4 RPP values (X 1/100) in each patient, there was no significant difference between DET-negatives and DET-positives (185.2 +/- 49.3 vs 157.4 +/- 32.4). Conversely, when considering the highest of the 4 RPP values in each patient, there was a significant difference between DET-negatives and DET-positives (280.3 +/- 63.9 vs 183.3 +/- 37.0; p less than 0.01). Thus, DET may provide a clinically useful tool for assessing in the individual the organic 'ceiling' of coronary reserve, by eliminating the variability in coronary tone, which may affect EST reproducibility and the correct evaluation of the impairment of organic coronary reserve.

Short term reproducibility of exercise testing in patients with ST segment elevation and different responses to the dipyridamole test.

The short term reproducibility of exercise testing in 25 patients who had exercise induced ST segment elevation without baseline regional asynergy or a previous myocardial infarction, who had different responses to the dipyridamole test, was assessed. The patients performed a dipyridamole echocardiography test and a second exercise stress test. All underwent coronary arteriography. Seventeen patients had transient regional asynergy after dipyridamole (group 1) and either ST segment elevation (14 patients) or depression (three patients); a second group of eight had no asynergy and no electrocardiographic changes (group 2). The repeated exercise stress test was positive in 16 of the 17 patients of group 1 (11 with ST elevation and five with ST depression) and in two patients of group 2 (both had ST depression and one had coronary artery disease). The dipyridamole echocardiography test was positive in 17 of the 19 patients with coronary artery disease and was negative in all six patients without coronary artery disease. The repeated exercise stress test was positive in 17 of the 19 patients with coronary artery disease and in one patient without. The dipyridamole echocardiography test and a repeated exercise stress test, but not a single exercise stress test, identified coronary artery disease causing exercise induced ST segment elevation.

Regional myocardial systolic function. Effects of coronary occlusion and reperfusion.

Intramyocardial pressure and segment length were measured during control conditions, during 30 sec coronary artery occlusion, and during reperfusion in the subendocardial (ENDO) and in the subepicardial (EPI) layers of the left ventricular wall, in 9 open-chest dogs. Under control conditions systolic subendocardial pressure, 179 +/- 11 mmHg, exceeded subepicardial pressure, 97 +/- 9 mmHg (P less than .001); the maximal rate of change of pressure in the subendocardium, 2231 +/- 170 mmHg/sec, was greater than in the subepicardium, 960 +/- 125 mmHg/sec, (P less than .001). Subendocardial systolic shortening, 23 +/- 2% was greater than subepicardial systolic shortening 16 +/- 1% (P less than .001). The maximal rate of systolic shortening in the subendocardium, 32 +/- 5 mm/sec, was also higher than in the subepicardial, 14 +/- 1 mm/sec (P less than .001). When the left anterior descending coronary artery was closed, subendocardial and subepicardial systolic pressures decreased immediately; conversely, appreciable changes in segment length were delayed 10-12 heart beats. After 30 sec of coronary occlusion a 35% reduction was observed in subendocardial and subepicardial systolic pressures, and systolic lengthening occurred. During reperfusion systolic shortening showed a brief overshooting and was back to control after 10 +/- 2 sec in subepicardium and 13 +/- 2 sec in subendocardium. Systolic intramyocardial pressure recovered in 14 +/- 3 sec in EPI and 18 +/- 2 sec in ENDO and subsequently rose above control level. Peak rebound occurred after 50-75 sec of reperfusion and was 27% higher than control in subendocardium and 20% in subepicardium. In 5 dogs the effects of coronary occlusions lasting 5, 15, 30, 45 and 60 sec were investigated. A progressive increase in ischemic depression and reperfusion rebound in subendocardial and subepicardial pressures was observed. These data show that subendocardial and subepicardial are both functionally depressed by coronary occlusion and that subendocardial and subepicardial both contribute to reperfusion hyperkinesis. Systolic intramyocardial pressures persist when shortening is abolished. Ischemic depression and reperfusion rebound of systolic intramyocardial pressures are affected by duration of coronary occlusion.

[Selective vasodilatation of the subepicardial coronary vasculature induced by carbochromen (author's transl)]. / Vasodilatazione selettiva della vascolatura coronarica sottoepicardica indotta dal carbocromene.

The effect of carbochromen on total and regional coronary blood flow was investigated in 6 anesthetized open-chest dogs. Total and regional myocardial blood flow was measured by radioactive microspheres, using the reference sample method. Left circumflex coronary flow was monitored by an electromagnetic flowmeter. In 4 dogs (Group 1) carbochromen was injected intravenously; in 2 dogs (Group 2) it was infused directly in the circumflex coronary artery. No significant changes in heart rate, left atrial left ventricular and aortic pressures were observed following carbochromen administration in both Groups. Left circumflex coronary blood flow progressively increased and a level slightly higher than peak reactive hyperemia was reached in both Groups. Regional myocardial blood flow measurements in Group 1 showed that the inner third of the left ventricular wall (ENDO) increased 2.7 times relative to control, the middle layer increased 3.4 times relative to control and the external third 4.5 times relative to control. A similar pattern was observed after intracoronary administration of carbochromen (Group 2). The ENDO/EPI flow ratio dropped from 0.98 +/- 0.16 to 0.58 +/- 0.18 in Group 1 and from 1.03 and 1.20 to 0.71 and 0.53 respectively in the two experiments of Group 2. Replacement of carbochromen with adenosine infusion in Group 2 produced a further increase in flow, mainly in the subendocardium resulting in ENDO/EPI flow ratio close to unity. These data demonstrate that the powerful coronary vasodilatory effect of carbochromen is not uniform being vasodilation more prominent in the vasculature of the external third of the left ventricular wall as compared to the inner third. Consequently a major redistribution of coronary blood flow, favouring the external layers of the left ventricle, results from carbochromen administration. This effect distinguishes carbochromen from other vasodilating stimuli than elicit a uniform response in the coronary vasculature and do not affect the ENDO/EPI ratio, including transient ischemia, adenosine, and dipyridamole.

Effect of dilazep on coronary and systemic circulations.

In order to assess the effects of dilazep on central hemodynamics and regional flows, 0.2 mg/kg of the drug were administered intravenously to 6 open-chest anesthetized dogs. Hemodynamic and flow measurements were performed under control conditions, and approximately 5, 10 and 25 min after treatment. Dilazep caused a marked and sustained reduction of coronary resistance and increased coronary blood flow. Flow increased uniformly in the subendocardial and subepicardial layers of the left ventricle so that no significant change occurred in the endo/epi flow ratio. Dilazep caused a significant reduction of total systemic resistance and aortic pressure, however flow to the liver, kidney and spleen was not reduced. We conclude that dilazep exerts a dilating action on the coronary and systemic arterial beds and increases uniformly regional myocardial blood flow. Dilazep does not alter the transmural distribution of coronary blood flow and does not impair kidney, liver and spleen perfusion.

Effects of dilazep on coronary and systemic hemodynamics in humans.

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.