[10-day clinical course of a stunned myocardium model with very short and repeated ischemias]. / Evolución a lo largo de 10 días de un modelo de miocardio aturdido mediante isquemias muy breves y repetidas.

INTRODUCTION AND OBJECTIVES: In previous studies we have observed ischemic processes of very brief duration (2 minutes) and with brief reperfusion (3 minutes), which have been repeated 20 times (ischemic protocol [IP]). They are capable of producing contractile dysfunction of the ischemic zone, with a decrease of 28.6% at 24 hours, and coronary blood flow maintenance (stunning). METHODS: The aim of this study is to examine the evolution of this dysfunction. The IP designed in our laboratory was used on 24 adult mongrel dogs. We measured regional myocardial function using a pair of implanted chronic ultrasonic crystals in the ischemic area (depending on the left anterior descending coronary artery) and a second pair in the control zone (depending on the left circumflex coronary artery). RESULTS: After analyzing results, we found that the shortening fraction decreased to 28.6% (p < 0.05) in 24 hours. During the subsequent five days the shortening fraction decreased to a minimum of 67.88% (p < 0.01), after which there was a progressive recovery that reached 18.95% (NS) below the base-line on the tenth day. We did not observe any significant variation in the hemodynamic parameters at any time. CONCLUSIONS: The repeated, very brief episodes of ischemia (in the experimental terms that we have explained) produced a contractile dysfunction which reached its maximum on the fifth day, and returned to normal on the tenth day. We hypothesize that these alterations could explain the episodes of left ventricular failure with spontaneous recuperation observed in stable myocardial ischemia, and for which no immediate cause has been found.

[Effects of L-carnitine on the regional function of the stunned myocardium caused by ischemia of short duration]. / Efectos de L-carnitina sobre la función regional del miocardio aturdido por isquemias de muy breve duración.

INTRODUCTION AND OBJECTIVES: Myocardial ATP is produced mainly by fatty acid oxidation, a process in which the fatty acid metabolite carrier carnitine is needed to carry the metabolites into the mitochondria. Cardiac ischemia is associated with carnitine depletion. Our objective was to study the functional effect of L-carnitine on myocardium stunned by very brief, repeated ischemias, and to examine its actions in the recovery period. METHODS: The two series studied were the control series (7 dogs) and the carnitine series (7 dogs). L-carnitine was administered to the carnitine series at doses of 250 mg/kg/day starting 7 days before the ischemic protocol and continuing during the follow-up period (10 and 15 days). The ischemic protocol consisted of 20 anterior descending coronary artery occlusions lasting 2 min and with 3 min of reperfusion between occlusions. Global and regional cardiac function parameters were recorded daily. RESULTS: No differences in the global functional (haemodynamic) or ECG of the two series were found, but there were differences in regional myocardial function. The control series segment shortening fraction fell to dyskinesis values during the occlusion periods, then recovered during reperfusions. The segment shortening fraction worsened during the stunning period, reaching its maximal impairment on the 5th day, after which it returned to basal values on the 15th day. The carnitine series showed the same performance in the occlusion/reperfusion period. However, during the stunning period the segment shortening fraction recovered and reached values close to the basal ones maintained them during the follow-up period. CONCLUSIONS: L-carnitine induces an almost immediate recovery of myocardial contractility, when it has been affected by very brief, repeated coronary occlusions. It limits the myocardial stunning apparition.

Effect of smoking on sudden and premature death.

BACKGROUND: Smoking has been related to coronary heart disease, and, in men, to sudden death. The results of a case-control study designed to assess the relationship between smoking and all causes of sudden and premature death are reported. METHODS: A questionnaire on the previous history and causes of death of all people buried in the Municipal Cemetery of Valencia (1986-1987) was administered to the relatives of the deceased. Among 4718 deaths, 284 victims of sudden death were identified, and 495 people who had not died suddenly were randomly sampled as controls. RESULTS: The proportion of smokers among the women studied was extremely low in contrast to 58.9% of men in the sudden death study group and 59.2% of men in the non-sudden death study group who smoked. Smokers died on average 10 years younger than non-smokers in the sudden-death group (63.3 +/- 12.3 and 73.3 +/- 11.0 years respectively; P < 0.001), and 8 years earlier in the non-sudden death group (68.5 +/- 13.3 and 76.8 +/- 13.2 years, respectively; P < 0.001). A logistic regression model showed that smokers had an adjusted relative risk of 0.81 for sudden death compared with non-smokers (95% confidence interval [CI]: 0.45-1.46). Smokers 65 years of age or under had a 2.7 times greater risk (95% CI: 1.49-5.04) of premature death than non-smokers. Similar results were found in patients from the coronary- and cardiac-death subgroups. CONCLUSIONS: Smoking is an independent risk factor for premature death but not for sudden death.

Mechanisms of ventricular arrhythmias in the presence of pathological hypertrophy.

Ventricular extrasystoles and the complex forms of non-malignant ventricular arrhythmias clearly increase in the presence of left ventricular hypertrophy. Left ventricular hypertrophy constitutes a clear sudden death risk factor. The connection between possible malignant arrhythmias, which have also been reported in LVH patients, and an increased incidence of sudden death has not been established. Hypertension, electrical changes in the hypertrophic myocyte, the growth of the collagen matrix and ischaemia (even in the absence of macro-angiographic injuries) are factors present in this group of patients that contribute to the appearance of arrhythmias. The arrhythmogenic substrate of LVH has to do with reentry mechanisms due to fibrillar stretching and anisotropy, as well as with self-sustaining activity triggered by after-potentials that depend on activation of slow calcium channels.

[Peripheral vascular reflexes during ventricular overdriving and cardiac ischemia. An experimental study]. / Reflejos vasculares periféricos durante sobreestimulación ventricular e isquemia cardíaca. Estudio experimental.

The aim of this paper is to analyze the behaviour of the muscular arteries during ventricular tachycardia in normal and in ischemic hearts. In 19/30 anaesthetized dogs in which a resistance vessel (gracilis muscle artery) was isolated (while innervation and venous backflow remained intact), we performed transient (20 min) coronary artery occlusions and ventricular overdriving (30 sec). A systolic left ventricular pressure decrease (144.2 +/- 18.2 mmHg vs 114 +/- 16.1) (p < 0.001) was produced with the coronary circumflex obstruction. Changes in the end-diastolic left ventricular pressure and muscular artery pressure were not significant. A new systolic left ventricular pressure decrease (114 +/- 16.1 mmHg vs 64.8 +/- 27) (p < 0.001) was induced when the ventricular overdriving (272.2 +/- 46.1 bpm) was added to the coronary circumflex obstruction. The end-diastolic left ventricular pressure increased (6.8 +/- 10.1 mmHg vs 18.3 +/- 4.8) (p < 0.001) and the muscular artery pressure increased (121 +/- 27.3 mmHg vs 158.1 +/- 21.3) (p < 0.01) in these circumstances. When the ventricular overdriving (275 +/- 70.7 bpm) was added to the left descendent anterior coronary occlusion a significative decrease of left systolic ventricular pressure (141 +/- 23 mmHg vs 84.4 +/- 28.4) (p < 0.01) and an increase of the muscular artery pressure (124.3 +/- 25 mmHg vs 149 +/- 25.1) (p < 0.01) was produced. Ventricular overdriving-induced hypotension produced an isolated muscular artery response with clear vasoconstrictor predominance, which indicates that there is a natural compensatory capacity with predominance of efferent sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Peripheral vascular reflexes in obstructions of the left ventricular outflow tract. Experimental study]. / Reflejos vasculares periféricos en las obstrucciones del tracto de salida del ventrículo izquierdo. Estudio experimental.

UNLABELLED: The aim of this work is to analyze the vascular tone behaviour of the muscular arteries in relation to the reflexes generated during aortic root obstruction when spontaneous heart rate is permitted and also with induced tachycardia. An experimental model used involved anaesthetized and intubated dogs in which a resistance vessel (gracilis muscle artery) was isolated, while innervation and venous backflow remained intact. Moderate (54.4 +/- 23.2 mmHg of mean increase in left ventricular pressure) and severe (240.1 +/- 92.5 mmHg) aortic obstructions for 30 s were provoked during spontaneous heart rate (n = 15) and during ventricular overdriving (n = 13) at 200, 250 and 300 bpm for 30 s. Ventricular overdriving at 200, 250, 300 and 400 bpm for 30 s without aortic root obstruction was induced in 20 dogs. Ventricular overdriving in intact hearts produced an initial decrease in the isolated muscular artery pressure of 12.0 +/- 7.2 mmHg (p < 0.01), 9.5 +/- 5.7 mmHg (p < 0.001), 13.6 +/- 8.6 mmHg (p < 0.001) and 14.3 +/- 8.7 mmHg (p < 0.01) at 200, 250, 300 and 400 bpm respectively followed by a recovery, so that at the end of overdriving (30 s), exceeded basal values in 11.9 +/- 10.0 mmHg (p < 0.05), 21.1 +/- 12.4 mmHg (p < 0.001), 21.9 +/- 10.4 mmHg (p < 0.001) and 36.1 +/- 21.3 mmHg (p < 0.001) for each overdriving rate respectively. Aortic obstruction during spontaneous heart rate produced and initial decrease in the isolated muscular artery pressure of 12.0 +/- 7.3 mmHg (p < 0.01), when the aortic obstruction were moderate, and 31.4 +/- 15.7 mmHg (p < 0.01) when the obstructions were severe, followed by a recovery of its basal values at the end of the obstruction time. Ventricular overdriving with aortic root obstruction did not produced significant changes in the isolated muscular artery pressure except in the highest rates of overdriving, that produced an increase of isolated muscular artery pressure of 23.9 +/- 16.2 mmHg (p < 0.01). IN CONCLUSION: ventricular overdriving-induced hypotension in intact hearts produces an isolated muscular artery response with clear vasoconstrictor predominance. Aortic obstruction-induced hypotension does not produce a vasoconstrictor response in the isolated muscular artery but rather an initial vasodilation response which does not revert to vasoconstriction at any point during the hypotensive process. Overdriving was not capable of inducing a peripheral vasoconstriction in presence of aortic root obstruction except in the highest rates of overdriving.