Brief Periods Of Myocardial Ischemia Research Articles

0576 Impact of Obstructive Sleep Apnea on In-Hospital Mortality Due to Acute Myocardial Infarction - A Large Retrospective National Study of Veterans

Abstract Introduction Ischemic preconditioning (IPC) is a phenomenon that refers to multiple, brief periods of myocardial ischemia followed by reperfusion. This counterintuitive preconditioning is thought to provide cardioprotection from subsequent prolonged ischemic events. Obstructive sleep apnea (OSA) may lead to IPC by frequent, recurrent short episodes of hypoxia and sympathetic stimulation. We hypothesized in patients who were admitted with acute myocardial infarction (MI), the presence of OSA was associated with improved survival during the hospitalization, likely due to IPC. Methods This is a retrospective cohort study utilizing national Veterans Health Administration (VHA) records. The cohort includes patients from 1999-2020 with a hospitalization for MI as the principal diagnosis. We confirm the OSA diagnosis using ICD9/10 codes. The primary outcome was in-hospital mortality during the index admission for acute MI. We reported the odds ratio (OR) of in-hospital mortality between with-OSA and without-OSA using logistic regression. We adjusted the OR (aOR) by age, gender, race, ethnicity, BMI, and Charlson Comorbidity index. Results Out of 4,237,444 veterans with any sleep diagnosis, 76,359 patients were hospitalized with a diagnosis of MI. We observed 30,116 with OSA (age, 64±10; BMI, 33±7) and 43,480 without OSA (age, 68±12; BMI, 29±6). The aOR of in-patient mortality was lower in with-OSA (n = 333[1.1%]; aOR, 1.86; 95% CI, 1.63 to 2.12) compared to without-OSA (n = 1,102[2.5%]; aOR, 2.02; 95% CI, 1.78 to 2.30). After stratifying the patients based on previous history of MI, the results remained the same. Conclusion We found that in patients admitted with acute MI, the OSA cohort was associated with lower mortality when compared to non-OSA cohort. We speculate that these differences may be attributed to IPC likely due to repetitive, chronic episodes of hypoxia in obstructive sleep apnea. Further research is warranted to elicit the clinical implications of ischemic preconditioning and OSA. Support (If Any) Culebras, A. Exploring the trail between cerebral ischemic aggravation and ischemic preconditioning. Obstructive sleep apnea leads the way. Sleep Medicine, Volume 67 ,2020, p 276-277Salman LA, Shulman R, Cohen JB. Obstructive sleep apnea, hypertension, and cardiovascular risk: epidemiology, pathophysiology, and management. Curr Cardiol Rep 2020;22(2):6

Electrical alternans induced by a brief period of myocardial ischemia during percutaneous coronary intervention: The characteristic ECG morphology and relationship to mechanical alternans

Electrical alternans (EA) has not been fully studied in the current percutaneous coronary intervention (PCI) procedure. The purpose of this study was to evaluate visible EA and the morphology of ST segment during PCI. The incidence of visible EA and ST-segment morphology were studied while the coronary artery was occluded for 20 seconds. When data were available, the relationship between EA and blood pressure was analyzed. The clinical and electrocardiographic data were compared with those of the age- and sex-matched controls. During balloon inflation, visible EA was observed in 5 of 306 patients (1.6%) in the last 2 years. EA was limited to PCI in the proximal left anterior descending artery. The ST segment elevated to 10.1 ± 3.2 mm, followed by an alternating QRS complex with a lower ST segment (5.6 ± 1.9 mm; P = .0047) with characteristic ST-segment morphology, which is known as lambda pattern. The mean age of the 5 patients was 68 ± 20 years, and 4(80%). were men. After the release of inflation, the ST-segment level returned rapidly to baseline, followed by normalization of J point. Compared with controls, the maximal elevated ST segment was significantly higher in patients with EA (5.7 ± 2.7 mm; P = .0028). The occlusion of the proximal left anterior descending artery with more severe ischemia seemed to be a prerequisite for developing EA. A higher ST segment was associated with a lower blood pressure and vice versa. A short period of ischemia during PCI may induce visible EA and alternating QRS complexes with a characteristic ST-segment morphology. A higher ST segment was associated with a lower blood pressure and vice versa.

Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease--a prospective study.

BackgroundIschemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease.Methods/DesignThis study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists.DiscussionIschemic preconditioning was first demonstrated by Murry et al. in dog’s hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning.Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It’s still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known.The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.

Man Overboard!

Man Overboard!

Design and synthesis of nitrate esters of aromatic heterocyclic compounds as pharmacological preconditioning agents

Ischemic preconditioning (IPC) constitutes an endogenous protective mechanism in which one or more brief periods of myocardial ischemia and reperfusion render the myocardium resistant to a subsequent more-sustained ischemic insult. Pharmacological preconditioning represents an ideal alternative of IPC. We now describe the design and synthesis of indole, quinoline, and purine systems with an attached pharmacophoric nitrate ester group. The indole and quinoline derivatives 4 and 5 possess structural features of the nitrate containing K ATP channel openers. Purine analogues 11 and 12, substituted at the position 6 by a piperidine moiety and at position 9 by an alkyl nitrate, could combine the effects of the nitrate containing K ATP channel openers and those of adenosine. Compound 13 bears the nicotinamide moiety of nicorandil instead of nitrate ester. Compounds 4, 5, and 11 reduced infarction and the levels of malondialdehyde (MDA) at reperfusion in anesthetized rabbits. Compounds 12 and 13 did not significantly reduce the infarct size. Analogues 4 and 5 increased cGMP and MDA during ischemia, while combined analogue 4 and mitoK ATP blocker 5-hydroxydecanoic acid (5-HD) abrogated this benefit suggesting an action through mitoK ATP channel opening. Treatment with derivative 11 combined with 5-HD as well as treatment with 11 and adenosine receptor blocker 8-( p-sulfophenyl)theophylline (SPT) did not abrogate cardioprotection. Compound 11 is a lead molecule for the synthesis of novel analogues possessing a dual mode of action through cGMP–mitoK ATP channel opening-free radicals and through adenosine receptors.

Redox regulation of ischemic preconditioning is mediated by the differential activation of caveolins and their association with eNOS and GLUT-4

Reactive oxygen species (ROS) generated during ischemia-reperfusion (I/R) enhance myocardial injury, but brief periods of myocardial ischemia followed by reperfusion [ischemic preconditioning (IP)] induce cardioprotection. Ischemia is reported to stimulate glucose uptake through the translocation of GLUT-4 from the intracellular vesicles to the sarcolemma. In the present study we demonstrated involvement of ROS in IP-mediated GLUT-4 translocation along with increased expression of caveolin (Cav)-3, phospho (p)-endothelial nitric oxide synthase (eNOS), p-Akt, and decreased expression of Cav-1. The rats were divided into the following groups: 1) control sham, 2) N-acetyl-L-cysteine (NAC, free radical scavenger) sham (NS), 3) I/R, 4) IP + I/R (IP), and 5) NAC + IP (IPN). IP was performed by four cycles of 4 min of ischemia and 4 min of reperfusion followed by 30 min of ischemia and 3, 24, 48 h of reperfusion, depending on the protocol. Increased mRNA expression of GLUT-4 and Cav-3 was observed after 3 h of reperfusion in the IP group compared with other groups. IP increased expression of GLUT-4, Cav-3, and p-AKT and p-eNOS compared with I/R. Coimmunoprecipitation demonstrated decreased association of Cav-1/eNOS in the IP group compared with the I/R group. Significant GLUT-4 and Cav-3 association was also observed in the IP group. This association was disrupted when NAC was used in conjunction with IP. It clearly documents a significant role of ROS signaling in Akt/eNOS/Cav-3-mediated GLUT-4 translocation and association in IP myocardium. In conclusion, we demonstrated a novel redox mechanism in IP-induced eNOS and GLUT-4 translocation and the role of caveolar paradox in making the heart euglycemic during the process of ischemia, leading to myocardial protection in a clinically relevant rat ischemic model.

Cardiac fibrinolytic capacity is markedly increased after brief periods of local myocardial ischemia, but declines following successive periods in anesthetized pigs

Fibrinolysis in blood is mainly reflected by the activities of tissue plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The effect of myocardial ischemia on their activities in the coronary circulation is, however, not established. With an improved experimental model, we therefore examined the effect of a brief period of myocardial ischemia on their activities. Furthermore, the consequences of repeated periods of ischemia, mimicking the situations in patients with unstable angina, were investigated. In six anesthetized pigs, we occluded the distal left anterior descending coronary artery (LAD) four times for 10 min with 40 min intervals and determined the activities of tPA and PAI-1 in arterial and coronary venous blood. By simultaneously recording LAD flow, we could estimate cardiac release of these factors at baseline conditions and during reperfusion. Neither net cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated during the experiment. However, a significant net release of tPA activity of 10.4 +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During reperfusion following the first period of ischemia, the cardiac release of tPA activity increased to a peak of 103 +/- 30-fold baseline release, but declined progressively after repeated periods of ischemia. After the fourth period, tPA release did not exceed an estimated baseline accumulation during ischemia and early reperfusion. In this porcine model, a substantial local increase in fibrinolytic capacity was observed after brief periods of ischemia, but declined subsequently by repeated periods of ischemia.

Reduced release of vasoconstrictors from the porcine heart after repeated periods of ischemia

ObjectiveTo examine if the decline in post-ischemic hyperemic flow after repeated brief periods of myocardial ischemia is accompanied by augmented cardiac release of the vasoconstrictors endothelin-1 (ET-1) and norepinephrine (NE).DesignMid-LAD (left anterior descending coronary artery) was occluded for 10 min with 30 min intervals a total of four times in six anesthetized pigs. Blood from the anterior interventricular coronary vein was drained through a shunt to the right atrium to facilitate blood sampling. Plasma concentrations of ET-1 and NE were repeatedly measured in arterial and coronary venous blood to estimate cardiac vasoconstrictor release.ResultsPlasma concentrations of ET-1 and NE remained unaltered, but cardiac release of both vasoconstrictors rose briefly during reperfusion due to the hyperemia. However, release declined progressively after repeated periods of ischemia and reperfusion and amounted to 53% (NE) and 17% (ET-1) of initial release after the fourth period of ischemia.ConclusionThe decline in post-ischemic hyperemia after repeated brief periods of myocardial ischemia is not accompanied by a progressive accentuation of cardiac ET-1 and NE release.

Myocardial injury and its prevention in the perioperative setting

Myocardial injury and its prevention in the perioperative setting

Journal-related Activities at the 2003 American Society of Anesthesiologists Annual Meeting

Journal-related Activities at the 2003 American Society of Anesthesiologists Annual Meeting

Calcium-independent phospholipase A(2) mediates CREB phosphorylation and c-fos expression during ischemia.

In isolated, perfused adult rat hearts, global ischemia increased the phosphorylation of cAMP response element-binding protein (CREB) relative to control levels, and this phosphorylation was reversed with reperfusion. CREB phosphorylation elicited by 5 min of global ischemia was sensitive to treatments with the calcium-independent phospholipase A(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) and occurred in the absence of increases in myocardial cAMP content. In contrast, CREB phosphorylation elicited by 15 min of global ischemia was likely mediated by elevated cAMP levels. The expression of c-fos, in response to brief myocardial ischemia, was also sensitive to BEL treatment. The induction of iPLA(2)-mediated CREB phosphorylation was further substantiated by the observations that lysoplasmenylcholine increased both the phosphorylation of CREB and the induction of c-fos expression in the absence and presence of BEL. CREB phosphorylation in both ischemic hearts and lysoplasmenylcholine-perfused hearts was inhibited by pretreatment of hearts with the specific cAMP-dependent protein kinase (PKA) inhibitor H-89. Taken together, these data demonstrate that iPLA(2) mediates CREB phosphorylation through a PKA-dependent pathway during brief periods of myocardial ischemia, possibly through the formation of lysophospholipids.

Effects of Ketamine and Its Isomers on Ischemic Preconditioning.

Effects of Ketamine and Its Isomers on Ischemic Preconditioning.Molojavyi et al. and Mullenheim et al.(page 623) and (page 630)Ischemic preconditioning, in which brief periods of myocardial ischemia followed by reperfusion provide protection from subsequent ischemic injury, has been shown to occur in animals as well as humans. Current evidence suggests that opening of the adenosine triphosphate–sensitive potassium channel is a key mechanism. Based on this evidence and the finding of a concentration-dependent inhibitory effect of ketamine on adenosine triphosphate–sensitive potassium channel activity, two research teams from the same institution investigated the effects of ketamine and its stereoisomers on preconditioning in animal models.In the first study, Molojavyi et al. subjected 80 isolated rat hearts to 30 min of no-flow ischemia followed by 60 min of reperfusion. The hearts were assigned randomly to one of 10 groups: two groups of eight hearts received no preconditioning stimulus before undergoing the study protocol; in another group of eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30-min ischemic period. In six treatment groups, ketamine, R (−)-ketamine, or S (+)-ketamine were administered at concentrations of 2 or 20 μg/ml before the preconditioning stimulus. A final group of eight hearts received 20 μg/ml R (−)-ketamine before ischemia. Left ventricular (LV) end-diastole pressure, LV developed pressure, and maximum and minimum dP/dt were obtained from digitized signals and later processed on a personal computer. LV end-diastole was determined as the point at which dP/dt started its rapid upstroke after crossing the zero line.Baseline LV developed pressure was similar in all groups of hearts. Those hearts in the control groups showed the poorest recovery of LV developed pressure, as well as a high creatine kinase release (evidence of cellular injury) after ischemia. Preconditioning improved recovery of LV developed pressure and reduced creatine kinase release. Administration of 2 μg/ml ketamine or 2 or 20 μg/ml S (+)-ketamine did not influence recovery of LV developed pressure. After 20 μg/ml ketamine or 2 or 20 μg/ml R (−) ketamine, the protective effects of preconditioning were abolished.In vivo , the pathophysiology of preconditioning and ischemia–reperfusion injury is more complex. Accordingly, Mullenheim et al. investigated the effects of ketamine and S (+)-ketamine on preconditioning in rabbit hearts in vivo . Forty-eight male New Zealand white rabbits were anesthetized with α-chloralose and instrumented for measurement of left ventricular pressure, cardiac output, and myocardial infarct size. Rabbits were assigned to one of five groups: a control group of 10 rabbits that received no pretreatment or conditioning before ischemia; a preconditioning group (n = 10) that underwent 30 min of coronary artery occlusion followed by 60 min of reperfusion; a group to which either 10 mg/kg ketamine (n = 9) or 10 mg/kg S (+)-ketamine (n = 8) was administered before preconditioning; and a final group of nine rabbits to which only 10 mg/kg−2ketamine was administered before ischemia. Two rabbits died during coronary artery occlusion, so the researchers were able to evaluate a total of 46 rabbits for analysis.All rabbits underwent 30 min of coronary occlusion, during which left ventricular pressure was reduced to 83 ± 14% of baseline values, and cardiac output was reduced to 84 ± 19% of baseline values. Functional recovery after 2 h of reperfusion did not differ significantly among groups. Infarct size (assessed by triphenyltetrazolium staining) was reduced from 45 ± 16% of the area at risk in controls to 24 ± 17% in the preconditioning group. Administration of ketamine had no effect on infarct size in animals without preconditioning but abolished the cardioprotective effects of preconditioning. S (+)-ketamine, however, had no effect, so the researchers conclude that the influence of ketamine on ischemic preconditioning is most likely enantiomer specific.

Ischemic preconditioning, myocardial stunning and anesthesia

Brief periods of ischemia have been shown to protect the heart against a subsequent prolonged ischemic insult, a phenomenon known as ischemic preconditioning. The protective effects of preconditioning markedly reduce myocardial ischemic injury in vivo. Volatile anesthetics have been shown to protect myocardium against infarction by a mechanism similar to that of ischemic preconditioning. Contractile dysfunction occurs after a brief period of myocardial ischemia, despite restoration of coronary blood flow in the absence of tissue necrosis. This process is known as myocardial stunning and has important clinical ramifications. Evidence indicates that adenosine triphosphate-regulated potassium channel function plays a central role in ischemic preconditioning, stunned myocardium, and in anesthetic-induced protection against ischemic injury.

Adenosine and cardioprotection in the diseased heart.

Biological and mechanical stressors such as ischemia, hypoxia, cellular ATP depletion, Ca2+ overload, free radicals, pressure and volume overload, catecholamines, cytokines, and renin-angiotensin may independently cause reversible and/or irreversible cardiac dysfunction. As a defense against these forms of stress, several endogenous self-protective mechanisms are exerted to avoid cellular injury. Adenosine, a degradative substance of ATP, may act as an endogenous cardioprotective substance in pathophysiological conditions of the heart, such as myocardial ischemia and chronic heart failure. For example, when brief periods of myocardial ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning. We found that ischemic preconditioning activates the enzyme responsible for adenosine release, ie, ecto-5'-nucleotidase. Furthermore, the inhibitor of ecto-5'-nucleotidase reduced the infarct size-limiting effect of ischemic preconditioning, which establishes the cause-effect relationship between activation of ecto-5'-nucleotidase and the infarct size-limiting effect. We also found that protein kinase C is responsible for the activation of ecto-5'-nucleotidase. Protein kinase C phosphorylated the serine and threonine residues of ecto-5'-nucleotidase. Therefore, we suggest that adenosine produced via ecto-5'-nucleotidase gives cardioprotection against ischemia and reperfusion injury. Also, we found that plasma adenosine levels are increased in patients with chronic heart failure. Ecto-5'-nucleotidase activity increased in the blood and the myocardium in patients with chronic heart failure, which may explain the increases in adenosine levels in the plasma and the myocardium. In addition, we found that further elevation of plasma adenosine levels due to either dipyridamole or dilazep reduces the severity of chronic heart failure. Thus, we suggest that endogenous adenosine is also beneficial in chronic heart failure. We propose potential mechanisms for cardioprotection attributable to adenosine in pathophysiological states in heart diseases. The establishment of adenosine therapy may be useful for the treatment of either ischemic heart diseases or chronic heart failure.

Attenuation of ischemia-induced activation of cardiac sympathetic afferents following brief myocardial ischemia in cats

Objective: We have previously shown that brief myocardial ischemia impairs neural conduction in cardiac sympathetic efferent fibers. However, attenuation of the activity of afferent sympathetic nerves, which may contribute to impaired ischemic nociception and reflex hemodynamic responses, is not well understood. Therefore, we studied the electrophysiological effects of brief myocardial ischemia on the mechano-, chemo- and ischemia-sensitive properties of cardiac sympathetic afferent fibers. Methods: Single unit activity of sympathetic afferent A δ and C fibers innervating the left ventricle (LV) was recorded from the thoracic chain or rami communicantes in 16 anesthetized cats. We tested the response of impulse activity to (1) mechanical LV probing, (2) epicardial application of bradykinin (10 μg), H 2O 2 (1.5%) or adenosine (500 μg), and (3) 1 min of coronary occlusion. Repeat tests were performed in 11 of 16 fibers after 15 min of coronary occlusion and 15 min of reperfusion. Control responses were measured in five fibers before and after a 30-min interval without ischemia. Results: Afferent fibers responded with increased activity to LV probing (16/16 fibers), bradykinin (13/16 fibers), H 2O 2 (7/11 fibers), adenosine (1/11 fibers), and to a 60 s period of coronary occlusion (11/16 fibers). The unit impulse activity to 1 min of coronary occlusion was markedly attenuated after 15 min of myocardial ischemia and 15 min of reperfusion ( P<0.05). This attenuation was associated with reduced sensitivity to mechanical and chemical stimuli, while in separate time-control studies ( n=5) no attenuation was observed in absence of ischemia. Conclusion: A brief period of myocardial ischemia is capable of attenuating mechano-, chemo- and ischemia-sensitive activity of cardiac afferent sympathetic nerves. This may have important implications for the mechanism of silent myocardial ischemia.

Priming of neutrophils after elective percutaneous transluminal coronary angioplasty is unrelated to accompanying brief myocardial ischemia

Objective: The purpose of this study was to investigate the effect of brief myocardial ischemia and vascular trauma induced by elective percutaneous transluminal coronary angioplasty on in vivo `priming' and activation of neutrophils. Patients and Methods: We studied 16 patients undergoing elective coronary angioplasty for symptomatic coronary artery disease and a control group of seven patients undergoing diagnostic cardiac catheterization. Free radical production from purified neutrophils (Ficoll–Hypaque density gradient method) was measured indirectly by the chemiluminescence method. Myocardial ischemia during balloon inflation was assessed by serial lactate determinations from coronary sinus and arterial blood. The degree of transient angioplasty-related myocardial ischemia was related to the oxidative response of activated neutrophils. Results: Mean (±S.E.M.) oxidative response, i.e. the lucigenin- and luminol-enhanced- chemiluminescence (counts per minute) of neutrophils sampled from the coronary sinus increased significantly after percutaneous transluminal coronary angioplasty (Lucigenin-chemiluminescence: pre-angioplasty 3.69±0.64×10 5 vs. post-angioplasty 7.08±1.2×10 5, P<0.01; Luminol-chemiluminescence: pre-angioplasty 2.81±0.67×10 6 vs. post-angioplasty 5.2±0.92×10 6, P<0.01). Twelve of 16 patients developed transient cardiac lactate production (mean coronary sinus lactate excess: +0.12 mmol/l) and three disclosed a lactate extraction ratio <10%, both suggestive of myocardial ischemia. However, there was no correlation between the cardiac lactate production and the increased oxidative response after coronary angioplasty ( r 2 (Lucigenin-chemiluminescence)=0.02, n.s.; r 2 (Luminol-chemiluminescence)=0.06, n.s.). Conclusion: `Priming' of neutrophils, as reflected by increased oxidative response, is likely to occur after coronary angioplasty, but not after the angiographic procedure itself. However, `priming' seems to be unrelated to the transient brief period of myocardial ischemia and rather depends on an alternative mechanism.

Cardiac sympathetic activity in response to acute myocardial ischemia.

Although experimental evidence has demonstrated that brief periods of myocardial ischemia are not associated with norepinephrine overflow from the heart, cardiac sympathetic responses to myocardial ischemia in humans remain unclear. Eleven patients undergoing angioplasty of the left anterior descending coronary artery had cardiac norepinephrine spillover measured immediately before inflation, during the final minute of a 5-min balloon inflation, and 1 min after deflation. Angioplasty caused significant S-T segment elevation and a reduction in the transcardiac lactate extraction ratio. Cardiac norepinephrine spillover was reduced from a mean value of 58 +/- 14 pmol/min at control to 41 +/- 15 pmol/min during balloon inflation and 38 +/- 14 pmol/min after deflation (P < 0.05 vs. control for both inflation and deflation values). In contrast, during balloon inflation, there were significant increases in arterial norepinephrine and epinephrine concentrations. Therefore, a brief period of myocardial ischemia caused by angioplasty of the left anterior descending coronary artery does not result in cardiac sympathetic activation, despite evidence of generalized sympathoadrenal activation.

Preconditioning

Preconditioning

Isoflurane-Induced Coronary Vasodilation Is Preserved in Reperfused Myocardium

Isoflurane causes vasodilation in the coronary circulation. The present study evaluated whether this action is preserved after a brief coronary occlusion followed by reperfusion. Fourteen open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery was perfused via an extracorporeal system with normal arterial blood or with arterial blood equilibrated with 1.4% (1 minimum alveolar anesthetic concentration [MAC]) isoflurane. Coronary perfusion pressure was maintained at 90 mm Hg. Coronary blood flow (CBF) was measured with a Doppler flow transducer. Steady-state changes in CBF during isoflurane, and during intracoronary infusions of acetylcholine (Ach; 20 micrograms/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP; 80 micrograms/min), an endothelium-independent vasodilator, were compared in normal myocardium and in myocardium subjected to 15 min of ischemia (due to cessation of perfusion) followed by 30 min of reperfusion. Ischemia-reperfusion had no significant effect on the increases in CBF by isoflurane (421% +/- 88% vs 388% +/- 84%) or SNP (115% +/- 18% vs 135% +/- 19%), whereas it attenuated these increases in CBF by Ach (232% +/- 38% vs 143% +/- 21%). In conclusion, a brief period of myocardial ischemia followed by reperfusion did not affect the coronary vasodilating effects of isoflurane and SNP, although it blunted these effects of Ach. The present findings provide further evidence suggesting that the ability of isoflurane to relax coronary vascular smooth muscle is independent of the nitric oxide-cyclic guanosine monophosphate pathway.

Bradykinin as an endogenous myocardial protective substance with particular reference to ischemic preconditioning--a brief review of the evidence.

The present brief review summarizes the evidence for the possibility that endogenously released bradykinin plays a major role in protecting the heart against the consequences of acute myocardial injury. This evidence includes the facts that kinins are generated under myocardial ischemia; that when they are administered, they are cardioprotective (e.g., antiarrhythmic); that drugs that enhance the release of bradykinin from the ischemic heart reduce the ischemic injury and, conversely, drugs that block bradykinin receptors attenuate the reduction in ischemic injury resulting from the release of, or administration of, bradykinin. The possible mechanism of bradykinin in the cardioprotection afforded by ischemic preconditioning is summarized. Ischemic preconditioning can be defined as the marked reduction in the severity of ischemic changes that result from coronary artery occlusion when that occlusion is preceded by brief periods of myocardial ischemia, either regional or global, induced, for example, by complete or partial coronary artery occlusion or by rapid ventricular pacing. The possible mechanisms of cardioprotection elicited by bradykinin (and ischemic preconditioning) are summarized. The most likely is the generation of cyclic GMP within the ischemic myocardium following bradykinin-stimulated nitric oxide generation and release from endothelial cells.