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17 beta-estradiol, administered acutely, protects ischemic myocardium in male rabbits. In the present study we investigated the effect of short-term estrogen on myocardial infarct size in oophorectomized female rabbits. We oophorectomized 24 sexually mature New Zealand white female rabbits. Twelve animals were left untreated and 12 received oral conjugated estrogens, 0.15 mg/day, for 4 weeks. At a second stage, a third group of 12 oophorectomized female rabbits was treated with intramuscular conjugated estrogens, 1 mg/day, also for 4 weeks. All rabbits underwent 30 minutes of coronary artery occlusion and 2 hours of reperfusion while on anesthesia with i.v. pentobarbital. Infarct and risk area were delineated by Zn-Cd fluorescent particles and tetrazolium chloride staining. The infarct size was expressed as a percentage of the risk zone (I/R %). Data are reported on 26 animals that survived the treatment period and the experiment. Heart rate, systolic, and mean blood pressure and double product did not differ between the three groups at baseline, ischemia, and reperfusion. The infarct size of the risk zone was significantly smaller in the intramuscular group compared with both the oral and the placebo group (18.5 +/- 3.5% vs. 41.3 +/- 9.2% and 43 +/- 8.4%, respectively, P = 0.03). Conjugated estrogens, administered intramuscularly at a high dose, protect ischemic myocardium in oophorectomized female rabbits.

Background and Hypothesis: In vitro studies have shown that atrial natriuretic peptide (ANP) causes relaxation of preconstricted blood vessel strips and inhibits the contraction of isolated vessels in response to norepinephrine and angiotensin II. The present study examined the effects of exogenous ANP on the coronary collateral blood flow during angioplasty., Methods: We studied 15 patients undergoing elective balloon angioplasty during the second and third balloon inflations. A Doppler flow guidewire was advanced distal to the lesion and used for the estimation of coronary blood flow velocity. After the second balloon inflation, 25 ng/kg/min of ANP were administered intracoronarily for 8 min. Electrocardiogram, pressure, and flow velocity were recorded immediately before each balloon deflation. Fourteen other patients served as controls and received normal saline infusion., Results: Velocity time integral increased from 65 +/- 40 to 79 +/- 46 mm (p < 0.05) during the third balloon inflation, whereas ST deviation decreased from 1.3 +/- 0.9 to 0.7 +/- 1.0 mV (p < 0.05). These variables did not change in the control group during the two tested balloon inflations., Conclusion: Exogenous ANP augments coronary collateral blood flow and ameliorates myocardial ischemia during angioplasty.

Objective: To examine the hypothesis that an altered left ventricular depolarization sequence may augment infarct size., Methods: Twenty-one New Zealand male rabbits were anesthetized and ventilated. The chest was opened and two electrodes were placed on the right atrium and ventricle. The rabbits were then randomized to atrial (n = 7), atrioventricular (AV) sequential (n = 7) or no (n = 7) pacing. The pacing rate was 20 beats/min higher than the sinus rate. After 1 min of pacing, the left coronary artery was occluded by a snare. After 30 mins, the snare was released and pacing was stopped. After 120 mins of reperfusion the experiment was terminated. Normal areas and areas at risk were delineated, infarct size was measured and the infarcted areas and areas at risk were planimetered., Results: All results were expressed in cubic centimetres, and the ratio of the infarcted area to area at risk was calculated as a percentage (%I:R). The double product during ischemia was 21,546 +/- 2300 in controls, 23,000 +/- 3005 in rabbits with atrial pacing and 24,418 +/- 4253 in rabbits with AV pacing (F = 1.33, P = 0.28), and %I:R was 41.4 +/- 19.8, 43.9 +/- 15.4 and 38.4 +/- 18.4 (F = 0.16, P = 0.84), respectively., Conclusions: An altered left ventricular depolarization sequence in rabbit hearts does not increase infarct size.

Although single or multiple bursts of ischemic preconditioning have been shown to protect against myocardial necrosis, the frequency-dependency of the protection afforded by multiple stimuli has not yet been systematically studied in the anesthetized animal. The aim of the present study was to characterize the effect of increasing numbers of preconditioning stimuli (5 min ischemia plus 10 min reperfusion) in a collateral-deficient species in vivo. Rabbits were anesthetized and divided into groups (n = 5-7/group) which were subjected to 0, 1, 2, 4, 6 or 8 cycles of preconditioning (each comprising 5 min of regional ischemia plus 10 min reperfusion) followed by 45 min of regional ischemia and 2 h reperfusion. An additional group, serving as a control, was subjected to eight cycles of preconditioning without a subsequent 45 min of regional ischemia. Infarct size (I) and risk zones (R) were delineated with the aid of tetrazolium staining and fluorescent particles and the I/R ratio was expressed as a percentage. Mean infarct size in the control group which had no preconditioning was 59.8 +/- 4.0%. This was reduced to 22.2 +/- 2.9%, 19.5 +/- 4.1% and 23.3 +/- 3.4% by one, two and four cycles of preconditioning. However, when the number of preconditioning cycles was increased to six or eight protection declined with infarct sizes of 41.8 +/- 6.9% (P < 0.05 v zero preconditioning control group) and 47.1 +/- 7.6% (N.S. v zero preconditioning control group). In the group subjected to eight cycles of preconditioning without subsequent ischemia, infarction was not detected. In conclusion, in the anesthetized rabbit, beyond 4 cycles, protection against infarction diminishes with increasing numbers of preconditioning cycles.

The aim of this study was to evaluate the way in which short-term protection declines and is eventually lost in preconditioning and to determine the efficacy of a second preconditioning at various reperfusion intervals. Male rabbits were divided into six groups. Forty-five minutes (sustained) ischemia followed by 120 minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute preconditioning (groups A, B, C, D, and E) and in a control group (F) after no preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A, 46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E, and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E, and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5-minute preconditioning stimuli, separated, respectively, by 45, 60, and 75 minutes of reperfusion; 10 minutes after the last preconditioning, the animals were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D (with the smaller and higher I/R ratio) were also incorporated into this protocol in order to compare the effect of the additional preconditioning with the single one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and 14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning declines gradually and is eventually lost. An additional preconditioning is always effective, and the longer the interval from the first preconditioning, the more potent is the effect.

The aim of this study was to investigate if levels of circulating cyclic guanosine monophosphate (c-GMP) alter in preconditioning. Twenty-eight rabbits were divided into four groups. In vivo hearts were preconditioned, either with 5 min (group A, n = 8) or with 1 min (group B, n = 8) ischemia, followed by 10 min reperfusion, while groups C (n = 7) and D (n = 5) had no interventions. Protection was determined by subjecting groups A, B and C (but not D) to 30 min regional ischemia which was followed (including group D) by 2 h reperfusion. Seven blood samples were collected for the assessment of circulating c-GMP at different points of time. All results were expressed in pmol/ml using radio-immunoassay and the infarcted to risk area in percent using fluorescent particles and tetrazolium chloride (TTC). Circulating c-GMP increased during long ischemia only in group A (baseline value 47 +/- 4, long ischemic values 60.5 +/- 4 and 60.4 +/- 4, p < 0.05). Circulating c-GMP in group A was significantly higher in the middle of the long ischemia in comparison to the groups B, C and D (60.5 +/- 4 vs 43.9 +/- 4, 45.8 +/- 5 and 43.6 +/- 4, p < 0.05). Infarcted to risk ratio was lower in group A than in groups B and C (12.2 +/- 4 vs 29.6 +/- 6 and 34.2 +/- 6 respectively, p < 0.05). Circulating c-GMP is increased in classically preconditioned in comparison to ineffectively preconditioned hearts or to control groups. This elevation may be related to the protective effect of this phenomenon.

We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 +/- 1.0 pmol/ml and 7.5 +/- 0.9 pmol/ml before angiography and balloon inflation to 11.1 +/- 1.3 pmol/ml at the maximum inflation (P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 +/- 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 +/- 1.7 pmol/ml and 17.5 +/- 1.7 pmol/ml, respectively) were lower than the highest value (22.1 +/- 2.1 pmol/ml) found 5 min after PTCA, (P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.

Endothelin-1 and cyclic guanosine monophosphate (c-GMP) peripheral vein plasma levels increase during coronary angioplasty, but the reason for this increase has not been elucidated. The purpose of this study was to investigate whether these changes are related to myocardial ischaemia, or to mechanical artery injury induced during the procedure. Thirty-two patients with stable angina pectoris and a single lesion were studied. They were aged 56 +/- 8 and were undergoing balloon angioplasty. Eight arteries were totally occluded and 24 were partially occluded. Blood samples were drawn from a peripheral vein after coronary artery engagement with the guiding catheter (baseline), after the first balloon inflation, immediately after the end of the procedure, and 4 h later. In the total occlusion group endothelin-1 increased by 7% (P ns), whereas in the partial occlusion group it increased by 45% after the procedure (P < 0.001). c-GMP in the partial occlusion group increased by 41% (P < 0.001) after the procedure whereas in the total occlusion group it increased by 5% (P ns). Thus, the increase in endothelin-1 and c-GMP peripheral vein plasma levels after coronary angioplasty is related to myocardial ischaemia rather than to mechanical artery injury.

The response of the contralateral arteries was investigated during balloon angioplasty of the left anterior descending artery. Thirty patients were studied. Coronary arteriograms were obtained at baseline, during maximal balloon inflation and at the end of the procedure. Luminal diameter was measured by a quantitative coronary arteriography analysis system. During balloon inflation the luminal diameter of the proximal segment of the right coronary artery increased by 2.4 +/- 6% (P < 0.05), and that of the left circumflex artery increased by 0.6 +/- 6% (P = ns). Both returned to near baseline values after angioplasty. In patients with increased collaterals during balloon inflation the left circumflex proximal segment increased more significantly than in patients with unchanged collaterals. The luminal diameter of the distal segment of the right coronary artery increased by 9 +/- 8% (P < 0.001) and that of the left circumflex artery by 8 +/- 11% (P < 0.01) during balloon inflation, returning to near baseline values after angioplasty. Thus, vasodilation of the contralateral arteries during balloon inflation at the time of coronary angioplasty occurs mainly in the distal segments, and appears to be related to an increase in collateral filling.

Classic ischemic preconditioning confers protection to the vulnerable myocardium following brief periods of ischemia with short intermittent periods of reperfusion. The aims of this study were: (i) to ascertain the protection from preconditioning using a relatively long reperfusion interval; (ii) to see whether this protection exists if preconditioning and long reperfusion is repeated and (iii) to evaluate the effect that an additional preconditioning stimulus has if it is given immediately before the sustained ischemia. Following anesthesia, in-vivo hearts were preconditioned with a 5 minute coronary ligation followed by 10 minutes reperfusion (Group A). This was compared to groups that were preconditioned with 5 minutes ischemia and 1 hour reperfusion (Group B); or 5 minutes ischemia with 1 hour reperfusion, repeated twice (Group C); or 5 minutes ischemia with 1 hour reperfusion repeated twice and followed by 5 minutes ischemia and 10 minutes reperfusion (Group D). Protection was assessed by subjecting each of the above groups to a further 45 minutes of regional ischemia followed by 120 minutes reperfusion. This protocol without prior preconditioning served as a control (Group E). The ratio of the infarcted to risk area was 23.1 +/- 4.1% in group A, 38.3 +/- 3.5% in group B, 58.4 +/- 4.9% in group C, 10.4 +/- 3.1% in group D and 61.8 +/- 6.2% in the control group E. Group D was significantly different from all the other groups. Group B was not different in comparison to the control group E. When a relatively long reperfusion period (Group B) was introduced the preconditioning protection diminished. When this long reperfusion period was repeated (Group C) overall protection was lost. However, when preconditioning was re-introduced alter a long delay (Group D), the protection afforded by it not only returned but appeared to be potentiated.

The aim of this study was to assess the effectiveness of chronic medical treatment with oral propranolol and its influence on heart rate variability in patients with vasovagal syndrome. A spectral frequency domain analysis was used for the estimation of heart rate variability characteristics. Thirty-six patients, mean age 49 +/- 17 years, with a history of recurrent syncope and positive tilt testing were involved in the study. All patients received oral propranolol (five patients also had a dual chamber inhibited DDI pacemaker implanted) for a mean time 12 +/- 6 months. One patient complained of syncope during this follow-up. The tilt test repeated in 29 patients during follow-up was negative in 28. In 20 patients treatment was discontinued for 4 days and a new tilt test was then performed. Eleven of these 20 patients (55%) had a positive test (P < 0.001 compared with the group in which treatment was continued). In the group of 11 patients in whom the tilt test became positive again after medical treatment had been withdrawn (mean age 43 +/- 20 years) and in 11 asymptomatic controls (mean age 52 +/- 19 years), with no history of syncope and negative tilt testing, the heart rate variability was assessed. The increase in the low frequency component from rest to the maximum value of heart rate variability during tilt testing was higher in the vasovagal group than in the controls (2.6 +/- 1.2 vs 1.5 +/- 0.7 P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated precordial ECG mapping (42 leads) and CK-MB serum measurements were done in 40 patients with anterior and/or anterolateral acute myocardial infarction. Twenty patients serving as controls, were treated with routine anticoagulant therapy. In 20 patients (the s group), randomly selected, a short-term IV infusion of 1,500,000 IU streptokinase was administered and followed by the same anticoagulant treatment as in controls. Ten subjects from each group underwent coronary arteriography one month later. From the analysis of ECG mapping the number of leads (N) and the sum of measurements (sigma) for each parameter were calculated. Before treatment there were no significant differences for all measured parameters between the two groups of patients. Seven days later, ST elevations were statistically different for NST and sigma ST with lower values for the s group. Higher values for NR and sigma R were also noted in this group. No statistically significant difference was found for NQ and sigma Q. CK-MB curve showed an earlier peak in the s group than in the control group. Five patients from the s group showed a patency of the infarct-related vessel. In conclusion, the results of this study show that patients receiving s have a significant benefit with ECG improvement. On the other hand, the CK-MB curve indicates an eventual recanalization to a certain degree in the obstructed coronary artery, which is the final goal.