Cold cardioplegia and the K+ channel modulator aprikalim (RP 52891): improved cardioprotection in isolated ischemic rabbit hearts

1994 ◽  
Vol 72 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Judith Pignac ◽  
Jean Bourgouin ◽  
Louis Dumont
Keyword(s):  
Coronary Flow ◽  
Left Ventricular ◽  
Protective Mechanism ◽  
Coronary Perfusion ◽  
Cardioplegic Solution ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
High K ◽  
Cold Cardioplegia ◽  
Channel Activator

Cellular potassium extrusion is now considered a natural protective mechanism following myocardial ischemia, and newly synthetized molecules mimicking cellular extrusion of K+ (potassium channel activators) appear promising for cardioprotection, although the underlying mechanisms for their beneficial effects have not been fully characterized. Indeed, the cardioprotective efficacy of K+ channel activators at low temperature or in the presence of the high K+ content of standard cardioplegic solution has never been addressed. Therefore the cardioprotective interaction of the thioformamide K+ channel activator aprikalim (RP 52891) and high K+ content, cold cardioplegia was studied in isolated ischemic rabbit hearts. Isolated hearts were perfused according to the Langendorff procedure at a constant pressure (85 cmH2O; 1 cmH2O = 98.1 Pa); systolic and diastolic left ventricular pressures, coronary flow, and heart rate were monitored throughout the study. Cardiac temperature was monitored through a thermocouple microprobe positioned in the left ventricular free wall. Global ischemia was carried out by completely shutting off the perfusate flow for 90 min, and reperfusion was monitored for 30 min. Several groups of isolated hearts (n = 6 per group) were treated before ischemia with either cold cardioplegia (St-Thomas' Hospital cardioplegic solution, 4 °C), aprikalim (10 μM), or glibenclamide (1 μM) alone, or with one of the following combinations: cold cardioplegia + aprikalim, cold cardioplegia + glibenclamide, or cold cardioplegia + both aprikalim and glibenclamide. A 10 μM infusion of aprikalim significantly increased coronary flow (33 to 63 mL/min, +90%) without negative chronotropic or inotropic effects. Aprikalim also completely reversed the coronary vasoconstrictive and cardiodepressant effects of glibenclamide, the ATP-sensitive K+ channel blocker, an indication of aprikalim's interaction on both coronary and myocardial K+ channels. Pretreatment with aprikalim significantly improved post-ischemic left ventricular function, compared with ischemia alone (93 ± 8 vs. 78 ± 6 mmHg (1 mmHg = 133.3 Pa) for ischemia alone, at 30 min of recovery), while at reperfusion, hyperemic coronary flow values were similar. Experiments carried out in the presence of glibenclamide suggested that the cardioprotective effects of aprikalim were related to activation of myocardial K+ channels rather than change in coronary perfusion. Cold cardioplegia alone significantly improved post-ischemic left ventricular recovery (99 ± 6 mmHg or 89% of pre-ischemic value at 30 min of reperfusion) despite the absence of hyperemic coronary flow. Aprikalim further improved, for the entire duration of reperfusion, the cardioprotection afforded by cold cardioplegia (post-ischemic systolic left ventricular pressure values were similar to pre-ischemic values). The latter additional improvement was blunted by glibenclamide, independently of coronary flow changes. These results indicated that the K+ channel activator aprikalim affords significant cardioprotection either alone or in the presence of cold cardioplegia; these beneficial properties appear to be independent of its coronary vasodilator effects. We thus conclude that aprikalim might be a significant addition to standard cardioprotection in cardiac surgery.Key words: aprikalim, glibenclamide, potassium channels, cardioprotection, coronary flow.

scholarly journals Arrhythmia analysis in Langendorff perfused hearts

2019 ◽  
Author(s):  
Hedvig Takács
Keyword(s):  
Heart Rate ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Observer Agreement ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Isolated Hearts ◽  
Definition Of

In this work, we used the isolated, Langendorff perfused heart model for arrhythmia investigations, and the data of the arrhythmia analysis served for clarifying and characterising the physiology of the model and also, to validate arrhythmia definitions. In our first investigation we examined the relationship between ventricular rhythm and coronary flow autoregulation in Langendorff perfused guinea pig hearts. It is a well-known fact, that heart rate affects coronary flow, but the mechanism is complex, especially in experimental settings. We examined whether ventricular irregularity influences coronary flow independently of heart rate. According to our results, during regular rhythm, left ventricular pressure exceeded perfusion pressure and prevented coronary perfusion at peak systole. However, ventricular irregularity significantly increased the number of beats in which left ventricular pressure remained below perfusion pressure, facilitating coronary perfusion. We found that in isolated hearts, cycle length irregularity increases the slope of the positive linear correlation between mean ventricular rate and coronary flow via producing beats in which left ventricular pressure remains below perfusion pressure. This means that changes in rhythm have the capacity to influence coronary flow independently of heart rate in isolated hearts perfused at constant pressure. In our second investigation we examined whether the arrhythmia definitions of Lambeth Conventions I (LC I) and Lambeth Conventions II (LC II) yield the same qualitative results and whether LC II improves inter-observer agreement. Data obtained with arrhythmia definitions of LC I and LC II were compared within and between two independent observers. Applying ventricular fibrillation (VF) definition of LC II significantly increased VF incidence and reduced VF onset time irrespective of treatment by detecting ‘de novo’ VF episodes. Using LC II reduced the number of ventricular tachycardia (VT) episodes and simultaneously increased the number of VF episodes, and thus, LC II masked the significant antifibrillatory effects of flecainide and the high K+ concentration. When VF incidence was tested, a very strong interobserver agreement was found according to LC I, whereas using VF definition of LC II reduced inter-observer agreement. It is concluded that LC II shifts some tachyarrhythmias from VT to VF class. VF definition of LC II may change the conclusion of pharmacological, physiological and pathophysiological arrhythmia investigations and may reduce inter-observer agreement.

Vasodilative and anti-adrenergic effects of adenosine in diabetic rat hearts

1992 ◽  
Vol 70 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Eve L. Warner ◽  
Franco Galasso ◽  
Carl I. Thompson ◽  
Francis L. Belloni
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Flow ◽  
Experimental Diabetes ◽  
Myocardial Contraction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Negative Inotropic Effects

To determine the vasodilative and negative inotropic effects of adenosine in hearts of diabetic rats, isolated hearts, perfused at constant perfusion pressure (Langendorff technique), were prepared from age-matched control Wistar rats and rats made diabetic 10 weeks prior to study by a single injection of streptozotocin (65 mg∙kg−1, i.p.). Adenosine and nitroprusside each increased coronary inflow when administered either as bolus injections or as infusions. Coronary flow responses to nitroprusside were unchanged in diabetic hearts. Coronary flow responses of diabetic hearts to adenosine injections were unchanged, but responses to adenosine infusions tended to be larger than in normal hearts. Diabetes had no significant effect on the EC50 for either vasodilator. Adenosine inhibited the inotropic effect of isoproterenol (enhanced left ventricular (LV) pressure (P) and LV dP/dtmax) in normal hearts, independently of its vasodilative action. This negative inotropic action of adenosine appeared equally strong in diabetic hearts. We conclude that adenosine's coronary vasodilative and anti-β-adrenergic, negative inotropic effects in the rat heart were not diminished after 10 weeks of streptozotocin-induced diabetes mellitus. Thus, earlier reports of diminished adenosine dilative efficacy in experimental diabetes may have been unique to those particular models.Key words: experimental diabetes mellitus, coronary, adenosine, isoproterenol, myocardial contraction.

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

Impairment of coronary flow reserve in aortic stenosis

2009 ◽  
Vol 106 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Damien Garcia ◽  
Paolo G. Camici ◽  
Louis-Gilles Durand ◽  
Kim Rajappan ◽  
Emmanuel Gaillard ◽  
...  
Keyword(s):  
Coronary Flow Reserve ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Lumped Parameter Model ◽  
Effective Orifice Area ◽  
Sensitivity Index ◽  
Coronary Perfusion ◽  
Flow Reserve ◽  
Wide Range

Coronary flow reserve (CFR) is markedly reduced in patients with severe aortic valve stenosis (AS), but the exact mechanisms underlying this impairment of CFR in AS remain unclear. Reduced CFR is the key mechanism leading to myocardial ischemia symptoms and adverse outcomes in AS patients. The objective of this study was to develop an explicit mathematical model formulated with a limited number of parameters that describes the effect of AS on left coronary inflow patterns and CFR. We combined the mathematical V3 (ventricular-valvular-vascular) model with a new lumped-parameter model of coronary inflow. One thousand Monte-Carlo computational simulations with AS graded from mild up to very severe were performed within a wide range of physiological conditions. There was a good agreement between the CFR values computed with this new model and those measured in 24 patients with isolated AS ( r = 0.77, P < 10−4). A global sensitivity analysis showed that the valve effective orifice area (EOA) was the major physiological determinant of CFR (total sensitivity index = 0.87). CFR was markedly reduced when AS became severe, i.e., when EOA was <1.0 cm2, and was generally exhausted when the EOA was <0.5–0.6 cm2. The reduction of CFR that is associated with AS can be explained by the concomitance of 1) reduced myocardial supply as a result of decreased coronary perfusion pressure, and 2) increased myocardial metabolic demand as a result of increased left ventricular workload.

Influence of coronary perfusion and myocardial edema on pressure-volume diagram of left ventricle

1961 ◽  
Vol 201 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Cecil E. Cross ◽  
P. Andre Rieben ◽  
Peter F. Salisbury
Keyword(s):  
Diastolic Pressure ◽  
Myocardial Edema ◽  
Ventricular Volume ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Similar Degree ◽  
Coronary Perfusion ◽  
Fluid Accumulation ◽  
Tension Development ◽  
Isolated Hearts

Pressure-volume diagrams of paced, isolated hearts were derived from isovolumic contractions and auxotonic contractions (simultaneous changes of pressure and volume). Coronary perfusion, fluid accumulation in heart muscle, and left ventricular volume and pressure were measured and controlled. Pressure-volume diagrams from isovolumic and auxotonic contractions were virtually identical in the same heart and were influenced by the same factors to a similar degree. At equal diastolic volumes the magnitude of systolic, as well as of diastolic pressures, and the occurrence of a systolic descending limb were directly related to coronary perfusion pressure. At equal diastolic volumes, other factors being constant, myocardial edema did not influence the contractile strength (i.e., maximum contractile tension development) of a ventricle, but did decrease its distensibility (i.e., increase diastolic pressure) in proportion to fluid accumulation. Myocardial water content and coronary factors (coronary arterial and venous pressures, coronary blood volume and flow) therefore constitute intrinsic mechanisms which can regulate the performance of a ventricle by changing its contractile strength, its distensibility, or both. The effects of coronary factors and of myocardial edema on the distensibility of a ventricle are sufficient in magnitude to explain hemodynamic abnormalities which characterize certain types of congestive heart failure.

scholarly journals Acute effects of nandrolone decanoate on cardiodynamic parameters in isolated rat heart

2016 ◽  
Vol 94 (10) ◽  
pp. 1048-1057 ◽  
Author(s):  
Tamara R. Nikolic ◽  
Vladimir I. Zivkovic ◽  
Ivan M. Srejovic ◽  
Dragan S. Radovanovic ◽  
Nevena S. Jeremic ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Albino Rats ◽  
Coronary Perfusion ◽  
Nandrolone Decanoate ◽  
Acute Effects ◽  
Isolated Rat

Despite worldwide use of anabolic steroids in last decades, there is still contradictory information about their acute influence on myocardium. The aim of this study was to examine the acute effects of nandrolone decanoate (ND) on cardiodynamics and coronary flow in isolated rat heart. The hearts of male Wistar albino rats (n = 48, 12 per group, age 8 weeks, body mass 180–200 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40–120 cmH2O). After the control sets of experiments, the hearts in different groups were perfused with different doses of ND (1, 10, or 100 μmol/L separately). Using a sensor placed in the left ventricle, we registered maximum and minimum rate of pressure development in the left ventricle (dP/dtmax and dP/dtmin), systolic and diastolic left ventricular pressure (SLVP and DLVP), and heart rate (HR). Coronary flow (CF) was measured flowmetrically. The results clearly show the depression in cardiac function caused by higher doses of ND. The highest concentration of ND (100 μmol/L) induced the most deleterious impact on the myocardial function and perfusion of the heart (coronary circulation), which could be of clinical significance.

Left ventricular heat production measured by coronary flow and temperature gradient

1961 ◽  
Vol 16 (5) ◽  
pp. 883-890 ◽  
Author(s):  
William A. Neill ◽  
Herbert J. Levine ◽  
Richard J. Wagman ◽  
Joseph V. Messer ◽  
Norman Krasnow ◽  
...  
Keyword(s):  
Temperature Gradient ◽  
Flow Rate ◽  
Heat Production ◽  
Coronary Flow ◽  
Coronary Circulation ◽  
Heat Removal ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Coronary Perfusion

The study of energetics of the left ventricular myocardium, normally based on its oxygen consumption and mechanical work performance, can be extended by determining its heat production as well. By considering all forms of energy input and output of the left ventricle, calculations were made of left ventricular net heat production under a variety of hemodynamic conditions. One of the mechanisms for removal of the heat produced is provided by the coronary blood, which is warmed in transit through the myocardium. Direct measurements of the rate of heat removal by the coronary circulation were made from coronary flow rate and veno-arterial temperature gradient. The fraction of left ventricular net heat production which is removed by the coronary perfusion is proportional to coronary flow rate. The fraction at a given flow rate is sufficiently reproducible to permit estimation of total heat produced from the portion measured in the coronary circulation. Certain of the theoretical applications of heat data may require more accuracy than appears feasible by this method. Which of the applications discussed will prove practical remains to be determined. Submitted on February 13, 1961

Improved Contractility and Coronary Flow in Isolated Hearts after 1-Day Hypothermic Preservation with Isoflurane Is Not Dependent on KATPChannel Activation 

1998 ◽  
Vol 88 (1) ◽  
pp. 233-244 ◽  
Author(s):  
David F. Stowe ◽  
Satoshi Fujita ◽  
Zeljko J. Bosnjak
Keyword(s):  
Coronary Flow ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Low Flow ◽  
Control Group ◽  
Protective Effects ◽  
Isolated Hearts ◽  
Time Control ◽  
O2 Extraction

Background Isoflurane protects against reperfusion injury in isolated hearts when given before, during, and initially after hypoxia or ischemia and aids in preconditioning hearts if given before ischemia. The aims of the current study were to determine if isoflurane is cardioprotective during 1-day, severe hypothermic perfusion and if a mechanism of protection is K(ATP) channel activation. Methods Guinea pig hearts (n = 60) were isolated, perfused with Kreb's solution initially at 37 degrees C, and assigned to either a nontreated warm, time control group or one of five cold-treated groups: drug-free cold control, 1.3% isoflurane, 1.3% isoflurane plus glibenclamide (4 microM), 2.6% isoflurane, or 2.6% isoflurane plus glibenclamide. Isoflurane and glibenclamide were given 20 min before hypothermia, during low-flow hypothermia (3.8 degrees C) for 22 h, and for 30 min after rewarming to 37 degrees C. Heart rate, left ventricular pressure, %O2 extraction, and coronary flow were measured continuously, and responses to epinephrine, adenosine, 5-hydroxytryptamine, and nitroprusside were examined before and after hypothermia. Results Each group had similar initial left ventricular pressures, coronary flows, and responses to adenosine, 5-hydroxytryptamine, and nitroprusside. Before hypothermia, isoflurane with or without glibenclamide increased coronary flow while decreasing left ventricular pressure and %O2 extraction. After hypothermia, left ventricular pressure and coronary flow were reduced in all cold groups but least reduced in isoflurane-treated groups. During normothermic perfusion after isoflurane and glibenclamide, left ventricular pressure, coronary flow, %O2 extraction, and flow responses to adenosine, 5-hydroxytryptamine, and nitroprusside were similarly improved in isoflurane and isoflurane-plus-glibenclamide groups over the cold control group but not to levels observed in the warm-time control group. Conclusion Isoflurane, like halothane, given before, during, and initially after hypothermia markedly improved but did not restore cardiac perfusion and function. Protective effects of isoflurane were not concentration dependent and not inhibited by the K(ATP) channel blocker glibenclamide. Volatile anesthetics have novel cardioprotective effects when given during long-term severe hypothermia.

Alpha 1-adrenergic blockade increases coronary blood flow during coronary hypoperfusion

1985 ◽  
Vol 249 (6) ◽  
pp. H1070-H1077 ◽  
Author(s):  
I. Y. Liang ◽  
C. E. Jones
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Adrenergic Blockade ◽  
Adrenergic Antagonist

Coronary hypoperfusion was elicited in alpha-chloralose-anesthetized open-chest dogs by reducing left coronary perfusion pressure to 50 mmHg. Left coronary blood flow, as well as left ventricular oxygen extraction, oxygen consumption, and contractile force were measured. The reduction in perfusion pressure caused significant reductions in coronary flow, oxygen consumption, and peak reactive hyperemic flow. During hypoperfusion in 11 dogs, intracoronary infusion of the specific alpha 1-adrenergic antagonist prazosin (0.1 mg/min) increased coronary flow and oxygen consumption by 22 and 16%, respectively. Peak increases were observed after 6–8 min of prazosin infusion (0.6–0.8 mg prazosin), and both increases were statistically significant (P less than 0.05). In seven additional dogs, beta-adrenergic blockade with propranolol (1.0 mg ic) did not significantly affect the actions of prazosin. In five additional dogs, the specific alpha 2-adrenergic antagonist yohimbine (1.3 mg ic) in the presence of propranolol (1.0 mg ic) did not affect coronary flow or oxygen consumption during coronary hypoperfusion. Those results suggest that an alpha 1- but not an alpha 2-adrenergic constrictor tone was operative in the left coronary circulation under the conditions of these experiments.

scholarly journals Effects of myocardial function and systemic circulation on regional coronary perfusion

2020 ◽  
Vol 128 (5) ◽  
pp. 1106-1122 ◽  
Author(s):  
Ravi Namani ◽  
Lik C. Lee ◽  
Yoram Lanir ◽  
Benjamin Kaimovitz ◽  
Sheikh M. Shavik ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Relaxation Rate ◽  
Coronary Flow ◽  
Myocardial Function ◽  
Regional Distribution ◽  
Systemic Circulation ◽  
Left Ventricular ◽  
Tree Structure ◽  
Coronary Perfusion ◽  
Ventricular Relaxation

We present a model of left ventricle perfusion based on an anatomically realistic coronary tree structure that includes its interaction with the systemic circulation. Left ventricular relaxation rate has a significant effect on the regional distribution of coronary flow and myocardial work.

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