Student survey after ten years of continuous blended teaching of echocardiography.

OBJECTIVE: To analyse the impact of 10 years of blended echocardiography teaching. METHODS AND RESULTS: A questionnaire was emailed to all medical doctors who graduated from the blended learning diploma in echocardiography developed by the University of Chile and taught by a team from Chile and Spain. One hundred and forty of the 210 students who graduated from the program between 2011 and 2020 completed the questionnaire: 53.57% were anaesthesiologists, and 26.42% were intensivists. More than 85% of respondents indicated that the online teaching met their expectations, and 70.2% indicated that the hands-on practice fulfilled the stated objectives. In a retrospective analysis using self-reported data, graduates reported that their use of transthoracic and transoesophageal echocardiography has increased from 24.29% to 40.71% and from 13.57% to 27.86%, repectively, after the programme compared to before the programme. They used echocardiography mainly in the perioperative period (56.7%) and during intensive care (32.3%), while only 11% of respondents used it in emergency care units. Nearly all (92.4%) respondents reported that the skills learned was very useful in their professional practice. CONCLUSIONS: Ten years after its launch, the blended learning diploma in echocardiography was well rated by graduate specialists, and is associated with a significant increase in the use of echocardiography in the perioperative period and during intensive care. The main challenges are to establish a longer period of practice and achieve greater implantation in emergency medicine.

Artículo de Revisión / The uncertainties of statistical "significance"

Statistical inference was introduced by Fisher and Neyman-Pearson more than 90 years ago to define the probability that the difference in results between several groups is due to randomness or is a real, "significant" difference. The usual procedure is to test the probability (P) against the null hypothesis that there is no real difference except because of the inevitable sampling variability. If this probability is high we accept the null hypothesis and infer that there is no real difference, but if P is low (P < 0.05) we reject the null hypothesis and infer that there is, a "significant" difference. However, a large amount of discoveries using this method are not reproducible. Statisticians have defined the deficiencies of the method and warned the researchers that P is a very unreliable measure. Two uncertainties of the "significance" concept are described in this review: a) The inefficacy of a P value to discard the null hypothesis; b) The low probability to reproduce a P value after an exact replication of the experiment. Due to the discredit of "significance" the American Statistical Association recently stated that P values do not provide a good measure of evidence for a hypothesis. Statisticians recommend to never use the word "significant" because it is misleading. Instead, the exact P value should be stated along with the effect size and confidence intervals. Nothing greater than P = 0.001 should be considered as a demonstration that something was discovered. Currently, several alternatives are being studied to replace the classical concepts.

[The uncertainties of statistical "significance"]. / Artículo de Revisión.

Statistical inference was introduced by Fisher and Neyman-Pearson more than 90 years ago to define the probability that the difference in results between several groups is due to randomness or is a real, "significant" difference. The usual procedure is to test the probability (P) against the null hypothesis that there is no real difference except because of the inevitable sampling variability. If this probability is high we accept the null hypothesis and infer that there is no real difference, but if P is low (P < 0.05) we reject the null hypothesis and infer that there is, a "significant" difference. However, a large amount of discoveries using this method are not reproducible. Statisticians have defined the deficiencies of the method and warned the researchers that P is a very unreliable measure. Two uncertainties of the "significance" concept are described in this review: a) The inefficacy of a P value to discard the null hypothesis; b) The low probability to reproduce a P value after an exact replication of the experiment. Due to the discredit of "significance" the American Statistical Association recently stated that P values do not provide a good measure of evidence for a hypothesis. Statisticians recommend to never use the word "significant" because it is misleading. Instead, the exact P value should be stated along with the effect size and confidence intervals. Nothing greater than P = 0.001 should be considered as a demonstration that something was discovered. Currently, several alternatives are being studied to replace the classical concepts.

[Ventricular contractility: Physiology and clinical projection]. / Contractilidad ventricular: Fisiología y proyección clínica.

The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future.

Contractilidad ventricular: fisiología y proyección clínica / Ventricular contractility: physiology and clinical projection

The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future.

Exercise preconditioning of myocardial infarct size in dogs is triggered by calcium.

We showed that exercise induces early and late myocardial preconditioning in dogs and that these effects are mediated through nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activation. As the intracoronary administration of calcium induces preconditioning and exercise enhances the calcium inflow to the cell, we studied if this effect of exercise triggers exercise preconditioning independently of its hemodynamic effects. We analyzed in 81 dogs the effect of blocking sarcolemmal L-type Ca channels with a low dose of verapamil on early and late preconditioning by exercise, and in other 50 dogs, we studied the effect of verapamil on NADPH oxidase activation in early exercise preconditioning. Exercise reduced myocardial infarct size by 76% and 52% (early and late windows respectively; P < 0.001 both), and these effects were abolished by a single low dose of verapamil given before exercise. This dose of verapamil did not modify the effect of exercise on metabolic and hemodynamic parameters. In addition, verapamil blocked the activation of NADPH oxidase during early preconditioning. The protective effect of exercise preconditioning on myocardial infarct size is triggered, at least in part, by calcium inflow increase to the cell during exercise and, during the early window, is mediated by NADPH oxidase activation.

Preconditioning tachycardia decreases the activity of the mitochondrial permeability transition pore in the dog heart.

Cardioprotection by preconditioning is a central issue of current research on heart function. Several reports indicate that preventing the assembly and opening of the mitochondrial permeability transition pore (mPTP) protects the heart against ischemia-reperfusion injury. We have previously reported that brief episodes of tachycardia decrease the infarct size produced by subsequent prolonged occlusion of a coronary artery, indicating that controlled tachycardia is an effective preconditioning manoeuvre. The effects of preconditioning tachycardia on mPTP activity have not been reported. Therefore, in this work we investigated if preconditioning tachycardia protects against calcium-induced mitochondrial swelling, a measure of mPTP activity. We found that tachycardia decreased by 2.5-fold the rate of mitochondrial calcium-induced swelling, a factor that presumably contributes to the cardioprotective effects of tachycardia. The oxidative status of the cell increased after tachycardia, as evidenced by the decrease in the cellular and mitochondrial GSH/GSSG ratio. We also observed increased S-glutathionylation of cyclophilin-D, an essential mPTP component, after tachycardia. This reversible redox modification of cyclophilin-D may account, al least in part, for the decreased mPTP activity produced by preconditioning tachycardia.

Late cardiac preconditioning by exercise in dogs is mediated by mitochondrial potassium channels.

We previously showed that exercise induces myocardial preconditioning in dogs and that early preconditioning is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels. We decided to study if late preconditioning by exercise is also mediated through these channels. Forty-eight dogs, surgically instrumented and trained to run daily, were randomly assigned to 4 groups: (1) Nonpreconditioned dogs: under anesthesia, the coronary artery was occluded during 1 hour and then reperfused during 4.5 hours. (2) Late preconditioned dogs: similar to group 1, but the dogs run on the treadmill for 5 periods of 5 minutes each, 24 hours before the coronary occlusion. (3) Late preconditioned dogs plus 5-hydroxydecanoate (5HD): similar to group 2, but 5HD was administered before the coronary occlusion. (4) Nonpreconditioned dogs plus 5HD: similar to group 1, but 5HD was administered before the coronary occlusion. Infarct size (percent of the risk region) decreased by effect of exercise by 56% (P < 0.05), and this effect was abolished with 5HD. 5HD by itself did not modify infarct size. Exercise did not induce myocardial ischemia, and the hemodynamics during ischemia-reperfusion period did not differ among groups. These effects were independent of changes in collateral flow to the ischemic region. We concluded that late cardiac preconditioning by exercise is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels.

Envejecimiento cardiovascular: [revisión] / Cardiovascular aging: [review]

Aging produces its own cardiovascular changes, mainly remodelling of arteries, heart and the microcirculation. These progressive changes, detected since adolescence, represent a major rísk factor for the development of cardiovascular diseases. Remodelling of arteries produces a thickening of the intima-media with fracture of elastic fibers and their replacement by collagen. These alterations induce an increase of the pulse wave and aortic impedance, with greater resistance to ventrícular ejection, that in turns induces the remodelling of the left ventricle. Ventricular remodelling leads to systolic, diastolic and chronotropic dysfunctions that explain the reduced capacity of old people to increase cardiac output during exercise. These alterations together with oxidative endothelial dysfunction and somatic mitochondrial mutations in the skeletal muscle decrease aerobic capacity, especially in adults aged >70 years. On the other hand, the transmission of an increased pulse wave to microvessels, mainly of the brain and kidneys, damage these organs. There is a search for candidate genes associated to this phenotype, especially those associated with arterial structure. Atpresent no specific treatment is available for cardiovascular aging. Exercise preserves a better aerobic capacity but does not prevent its decline with age. Vasodilator drugs may decrease aortic impedance and perhaps delay remodelling. However there is no clinical evidence available to recommend these drugs in young healthy people. Finally new drugs that modify aortic molecular structure are been investigated.

[Cardiovascular aging]. / Envejecimiento cardiovascular.

Aging produces its own cardiovascular changes, mainly remodelling of arteries, heart and the microcirculation. These progressive changes, detected since adolescence, represent a major risk factor for the development of cardiovascular diseases. Remodelling of arteries produces a thickening of the intima-media with fracture of elastic fibers and their replacement by collagen. These alterations induce an increase of the pulse wave and aortic impedance, with greater resistance to ventricular ejection, that in turns induces the remodelling of the left ventricle. Ventricular remodelling leads to systolic, diastolic and chronotropic dysfunctions that explain the reduced capacity of old people to increase cardiac output during exercise. These alterations together with oxidative endothelial dysfunction and somatic mitochondrial mutations in the skeletal muscle decrease aerobic capacity, especially in adults aged >70 years. On the other hand, the transmission of an increased pulse wave to microvessels, mainly of the brain and kidneys, damage these organs. There is a search for candidate genes associated to this phenotype, especially those associated with arterial structure. At present no specific treatment is available for cardiovascular aging. Exercise preserves a better aerobic capacity but does not prevent its decline with age. Vasodilator drugs may decrease aortic impedance and perhaps delay remodelling. However there is no clinical evidence available to recommend these drugs in young healthy people. Finally new drugs that modify aortic molecular structure are been investigated.

Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection.

AIM: Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase to (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) the preconditioning effects of exercise and tachycardia on infarct size following coronary artery occlusion. METHODS AND RESULTS: We measured NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release kinetics in sarcoplasmic reticulum (SR) vesicles isolated from dog ventricular muscle after exercise and tachycardia, plus or minus prior administration of the NADPH oxidase inhibitor apocynin. In ventricular muscle sections, we studied the colocalization of NADPH oxidase and RyR2 by confocal microscopy using fluorescent antibodies. We determined the effect of apocynin on the infarct size produced by occlusion of the descendent anterior coronary artery in animals preconditioned by exercise or tachycardia. Exercise and tachycardia increased NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release rates in isolated SR vesicles. Cardiac muscle sections displayed significant colocalization of NADPH oxidase and RyR2, suggesting direct and specific effects of reactive oxygen species (ROS) produced by NADPH oxidase on RyR2 activation. The NADPH oxidase inhibitor apocynin prevented the increase in RyR2 S-glutathionylation, reduced calcium release activity, and completely prevented the protective effects of exercise and tachycardia on infarct size. CONCLUSIONS: The loss of cardioprotection induced by the NADPH oxidase inhibitor suggests that ROS generated by this enzyme are important mediators of the preconditioning response, which presumably involves NADPH oxidase-induced RyR2 S-glutathionylation.

Participación de Ca2+ en el precondicionamiento del miocardio por ejercicio / Role of Ca2+ in exercise induced myocardial preconditioning

Antecedentes: Episodios breves de ejercicio previos a la oclusión prolongada de una arteria coronaria disminuyen el tamaño del infarto inducido por ésta. Objetivo: Dado que la administración intracoronaria de Ca2+ induce precondicionamiento, y el ejercicio probablemente aumenta el calcio citosólico, decidimos estudiar si el precondicionamiento por ejercicio está mediado por Ca2+. Material y método: Para ello analizamos el efecto del bloqueo de los canales de calcio del sarcolema, con verapamilo, sobre la acción precondicionante del ejercicio. Se midió tamaño del infarto en perros entrenados a correr en cinta sin finasignados aleatoriamente a los siguientes grupos. I: Isquemia inducida por oclusión coronaria durante 1 hora seguida de reperfusión por 4 hrs. E+I: Similar al grupo I, pero los perros hicieron ejercicio antes de inducir la isquemia. V+I: Similar al grupo I, pero se administró verapamilo antes de inducir la isquemia. V+E+I : Similar al grupo E+I, pero se administró verapamilo antes del ejercicio. Para estudiar el posible rol mediador del retículo sarcoplasmático (RS) en los efectos de la isquemia y de verapamilo, se midió la captación y la liberación de calcio en vesículas de RS de la pared del ventrículo izquierdo sometida a isquemia con o sin verapamilo en perros con y sin precondicionamiento con ejercicio. Los resultados, expresados como promedio +/- ES, se analizaron mediante ANOVA seguido del test de Holm para comparaciones múltiples. Resultados: Verapamilo revirtió el efecto protector del ejercicio sobre el tamaño del infarto (E+I: 6,0 +/- 9,4; N=12 vs V+E+I: 27,7+/-9,6; N=15; P<0.05), pero no modificó el efecto protector del ejercicio precondicionante sobre los trastornos de transporte de calcio en el RS inducidos por la isquemia. Conclusiones: Nuestros resultados sugieren que el precondicionamiento inducido por ejercicio está mediado por la entrada de calcio a la célula...

Background: Brief episodes of exercise prior to a prolonged occlusion of a coronary artery substantially reduce infarct size. Aim: Since the intracoronary administration of Ca2+ induces preconditioning and exercise most likely increases cytosolic calcium we put forward the hypothesis that preconditioning by exercise is mediated by calcium. Methods: For this purpose we analyzed the effect of verapamil, a sarcolemmal calcium channel blocker, on preconditioning by exercise. We measured infarct size in dogs randomly assigned to one of the following groups. I: Ischemia induced by coronary occlusion during 1 hour followed by reperfusion during 4 hours. E+I: Similar to group I, but the dogs run on a treadmill prior to ischemia. V+I: Similar to group I but verapamil was administered before the coronary occlusion. V+E+I: Similar to group E+I but verapamil was administered before exercise. SR vesicles from ventricular tissue were isolated from dogs subjected to the same experimental protocols and calcium release and active calcium uptake were measured. Results were expressed as Mean +/- SE and analyzed by ANOVA followed by Holm test for multiple comparisons. Results: Verapamil reverted the protective effect of exercise on infarct size (E+I: 6,0 +/- 9,4; N=12 vs V+E+I: 27,7 +/- 9,6;N=15; P<0.05) however it did not modify the protective effect of exercise on the alterations produced by ischemia on calcium transport in the RS. Conclusions: These results suggest that the preconditioning effect of exercise is mediated by calcium entering the cell through the sarcolemma but not by exercise effects on SR calcium transport.

Tachycardia increases NADPH oxidase activity and RyR2 S-glutathionylation in ventricular muscle.

We have shown previously that electrically induced tachycardia effectively produces myocardial preconditioning. Among other effects, tachycardia increases calcium release rates in microsomal fractions enriched in sarcoplasmic reticulum (SR) isolated from dog cardiac ventricular muscle. Here, we report that preconditioning tachycardia increased twofold the NADPH oxidase activity of isolated SR-enriched microsomal fractions, measured as NADPH-dependent generation of superoxide anion and hydrogen peroxide. Tachycardia also augmented the association of rac1 and the NADPH oxidase cytosolic subunit p47(phox) to the microsomal fraction, without modifying the content of the membrane integral subunit gp91(phox). Microsomes from control animals displayed endogenous S-glutathionylation of cardiac ryanodine receptors (RyR2); in microsomal fractions isolated after tachycardia RyR2 S-glutathionylation levels were 1.7-fold higher than in controls. Parallel in vitro experiments showed that NADPH produced a transient increase in calcium release rates and enhanced 1.6-fold RyR2 S-glutathionylation in control microsomes but had marginal or no effects on microsomes isolated after tachycardia. Catalase plus superoxide dismutase, and the NADPH oxidase inhibitors apocynin and diphenyleneiodonium prevented the in vitro stimulation of calcium release rates and RyR2 S-glutathionylation induced by NADPH, suggesting NADPH oxidase involvement. Conversely, addition of reducing agents to vesicles incubated with NADPH markedly inhibited calcium release and prevented RyR2 S-glutathionylation. We propose that tachycardia stimulates NADPH oxidase activity, which by enhancing RyR2 redox modifications such as S-glutathionylation, would contribute to sustain faster calcium release rates during conditions of increased cardiac activity. This response may be an important component of tachycardia-induced preconditioning.

Effect of tachycardia on myocardial sarcoplasmic reticulum and Ca2+ dynamics: a mechanism for preconditioning?

We have previously demonstrated that brief episodes of tachycardia prior to a prolonged occlusion of a coronary artery, followed by reperfusion, substantially reduce the infarct size. Adenosine receptors and mitochondrial ATP-dependent K(+) channels mediate this effect. Since preconditioning can be induced or reverted by maneuvers that increase or decrease [Ca(2+)](i), respectively, and tachycardia increases [Ca(2+)](i), we studied the participation of sarcoplasmic reticulum and Ca(2+) in the preconditioning effect of tachycardia. We measured the effect of ischemia and tachycardia on Ca(2+) uptake and release by sarcoplasmic reticulum vesicles isolated from left ventricular canine myocardium. Myocardial ischemia increased Ca(2+)-release rate constants and decreased both the initial rates of Ca(2+) uptake and [(3)H]-ryanodine binding by sarcoplasmic reticulum. In addition, ischemia induced a decrease in the pentameric form of phospholamban and in the content of ryanodine-receptor Ca(2+)-release channel protein. All these effects were reverted in hearts preconditioned with tachycardia. Furthermore, tachycardia by itself increased [(3)H]-ryanodine binding, Ca(2+)-release rate constants and the protein levels of ryanodine-receptor Ca(2+)-release channels and the ATP-dependent Ca(2+) pump. These results suggest that tachycardia preserves the integrity of the sarcoplasmic reticulum preventing the excess of release and the decrease of uptake of Ca(2+) produced by ischemia, thereby avoiding cytosolic Ca(2+) overload. This sarcoplasmic reticulum protection could partly explain the preconditioning effect of tachycardia.

Exercise induces early and late myocardial preconditioning in dogs.

OBJECTIVE: We tested the hypothesis that exercise induces myocardial preconditioning in dogs. METHODS: We instrumented dogs with a snare on the anterior descending coronary artery and catheters in the root of the aorta, left ventricular cavity and coronary sinus. After recovering from surgery the dogs were trained to stay in the laboratory and run on a treadmill. Subsequently, they were randomly allocated to five groups: (1) non-preconditioned dogs: under anesthesia, the anterior descending coronary artery was occluded during 1 h and then reperfused during 4.5 h. (2) Early preconditioned dogs: procedure similar to group 1 but the dogs performed exercise on a treadmill for five periods of 5 min each before the coronary occlusion. (3) Late preconditioned dogs: procedure similar to group 2 but 24 h were allowed to elapse between the preconditioning exercise and the coronary occlusion. (4) Early preconditioned dogs plus 5-hydroxydecanoate: procedure similar to group 2 but 5-hydroxydecanoate was administered prior to exercise. (5) Non-preconditioned dogs with 5-hydroxydecanoate: procedure similar to group 1 but 5-hydroxydecanoate was administered at a time equivalent to that in group 4. RESULTS: Exercise did not induce myocardial ischemia and the hemodynamics during the experiments did not differ between groups. Exercise immediately before the coronary occlusion decreased the infarct size (percent of the risk region) by 78% (P<0.05), an effect that was abolished with 5-hydroxydecanoate. Exercise 24 h prior to coronary occlusion decreased infarct size by 46% (P<0.05 vs. non-preconditioned dogs, P<0.05 vs. early preconditioned dogs). 5-Hydroxydecanoate by itself did not modify infarct size. These effects could not be explained by changes in collateral flow to the ischemic region. CONCLUSIONS: Exercise prior to a coronary occlusion induces early and late preconditioning of the infarct size. The early effect is mediated through mitochondrial ATP-sensitive potassium channels.

Efecto de la activación y el bloqueo beta adrenérgico sobre la distensibilidad ventricular del miocardio isquémico / Effects of activation and beta adrenergic block on the ventricular distensibility during miocardial ischemia

La isquemia cardíaca disminuye la distensibilidad y velocidad de relajación ventricular. Debido al uso frecuente de fármacos beta adrenérgicos en pacientes con isquemia cardíaca, nosotros estudiamos el efecto de la activación y del bloqueo beta adrenérgico sobre la distensibilidad y la velocidad de relajación del ventrículo izquierdo del perro mediante las curvas de presión ventricular diastólica-longitud de segmento (PVD-LS) y la constante de tiempo de relajación (T), respectivamente. La isquemia miocárdica desplazó la curva PVD-LS por aumento de PVD sin cambio de LS. La presión ventricular de fin de diástole (PVFD) aumentó de 7 ñ 0.6 a 15.2 ñ 1.4 mm Hg (p <0.001) y T aumentó de 25 ñ 5.5 a 36.7 ñ 7.5 m. s. (p<0.02). Propranolol, en presencia de isquemia, desplazó aun más la curva PVD-LS y aumentó PVFD 22.4 ñ 4.4 mm Hg (p<0.02) y T a 54.7 ñ 9.6 m.s. (p<0.02). Isoproterenol, en cambio, revirtió el efecto de la isquemia; desplazó la curva PVD-LS hacia la posición control y disminuyó PVFD a 6.8 ñ 0.8 mm Hg (p<0.001) y T a 19.8 ñ 4.3 m.s. (p<0.05). Estos resultados demuestran que la disminución de distensibilidad y velocidad de relajación miocárdica producida por la isquemia son exacerbadas o contrarrestadas por el bloqueo o activación beta adrenérgica, respectivamente

Effects of alpha-1 adrenergic blockade on regional flow in the ischemic heart

Aunque la isquemia induce una poderosa vasodilatación coronaria, persiste un tono vasoconstrictor alfa en el miocardio isquémico. Con el fin de determinar si este tono vasoconstrictor es mediado por receptores alfa, nosotros medimos el flujo coronario con microesferas radiactivas en el ventrículo izquierdo normal e isquémico del perro, antes y durante el bloqueo alfa-1 adrenérgico con trimazosin. La isquemia se produjo disminuyendo la presión de perfusión coronaria a 22 ñ 1.4 mmHg. La frecuencia cardíaca y la presión arterial se mantuvieron constantes en cada experimento. Trimazosin aumentó el flujo significativamente en la pared ventricular normal, en mayor proporción en el subepicardio que en el subendocardio produciendo una disminución del cociente del flujo subendocárdico/subepicárdico de 1.38 ñ 0.12 a 1.20 ñ 0.11 (p < 0.05). En la región isquémica Trimazosin no modificó el flujo transmural, pero disminuyó el flujo en el subendocardio y lo aumentó en el subepicardio con la consiguiente disminución del cociente de flujo subendocárdico/subepicárdico de 0.63 ñ 0.09 a 0.38 ñ 0.06 (p < 0.01). Estos resultados muestran que en el miocardio isquémico persiste un tono vasoconstrictor mediado por receptores alfa-1 adrenérgicos, y el bloqueo de éstos deteriora la perfusión del subendocardio