Calcitonin gene-related peptide does not interact with sympathetic activity in myocardial ischemia

The aim of the present study was to assess whether calcitonin gene-related peptide (CGRP) modulates exocytotic norepinephrine release in ischemic myocardium. In isolated rat hearts subjected to 30 min of low flow ischemia, CGRP release increased 2.8-fold whereas stimulation-induced norepinephrine release decreased 4.1-fold. Pretreatment of rats with capsaicin almost completely depleted cardiac CGRP stores; however, suppression of norepinephrine release by 30 min of low flow ischemia was not affected. At normal flow, exogenous CGRP (5 micromol l-1) had no effect on norepinephrine release. These findings suggest that CGRP release from sensory neurons does not interact with the cardiac sympathetic system during myocardial ischemia.     

Inhibition of nonexocytotic norepinephrine release by desipramine reduces myocardial infarction size

During myocardial ischemia, a substantial accumulation of norepinephrine occurs in the ischemic zone due to a local nonexocytotic release of norepinephrine. Norepinephrine release is driven by the neuronal monoamine transporter (NET), which reverses its usual transmembrane transport direction. We investigated whether this local accumulation of norepinephrine contributes to irreversible myocardial injury in an in vivo model of myocardial infarction. Male, anaesthetized Wistar rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. Five minutes prior to coronary occlusion, the NET inhibitor desipramine was administered intravenously. Infarct size (IS) was determined by TTC-staining and was related to the area at risk (AAR). The influence of desipramine on cardiac norepinephrine release was investigated in isolated perfused hearts with 30 min of regional ischemia. Norepinephrine was measured in the effluent from the hearts by HPLC and electrochemical detection. Desipramine (0.1-0.8 mg/kg) dose-dependently reduced infarct size (IS/AAR) from 0.54 to 0.21 and suppressed postischemic norepinephrine release from 245 to 108 pg/mL. In summary, the data indicate that nonexocytotic release of norepinephrine in myocardial ischemia exaggerates acute ischemic damage, because suppression of ischemia-induced release of norepinephrine by the tricyclic antidepressant desipramine effectively reduces infarct size in an in vivo model of myocardial ischemia.     

Validity of elevated interstitial levels of taurine as a predictor of myocardial ischemic injury

Summary. The microdialysis (MD) technique allows for continuous in vivo monitoring of dynamic changes in the interstitial levels of energy-related metabolites. The release of taurine from the myocyte has been suggested as a marker of ischemic injury. The relationship between (interstitial) taurine release and the degree of myocardial ischemic injury was evaluated following a 40min long ischemia in a porcine heart-infarct-model. Different protocols of ischemia and reperfusion were used in order to achieve a graded level of myocardial injury. Both interstitial peak levels and the area under curve of taurine obtained during ischemia and reperfusion correlated with the degree of ischemic injury (assessed by developed infarct size estimation). The release of taurine in the myocardium measured by the MD-technique correlated with the degree of ischemic injury during ongoing ischemic insult. Hence, taurine determination in the MD-setting represents a powerful tool to follow the development of myocardial ischemic injury over time.     

Proteomics of ischemia and reperfusion injuries in rabbit myocardium with and without intervention by an oxygen-free radical scavenger

A brief period of ischemia followed by timely reperfusion may lead to prolonged, yet reversible, contractile dysfunction (myocardial stunning). Damage to the myocardium occurs not only during ischemia, but also during reperfusion, where a massive release of oxygen-free radicals (OFR) occurs. We have previously utilized 2-DE and MS to define 57 protein spot changes during brief ischemia/reperfusion (15 min ischemia, 60 min reperfusion; 15I/60R) injury in a rabbit model (White, M. Y., Cordwell, S. J., McCarron, H. C. K., Prasan, A. M. et al., Proteomics 2005, 5, 1395-1410) and shown that the majority of these occur because of physical and/or chemical PTMs. In this study, we subjected rabbit myocardium to 15I/60R in the presence of the OFR scavenger N-(2-mercaptopropionyl) glycine (MPG). Thirty-seven of 57 protein spots altered during 15I/60R remained at control levels in the presence of MPG (15I/60R + MPG). Changes to contractile proteins, including myosin light chain 2 (MLC-2) and troponin C (TnC), were prevented by the addition of MPG. To further investigate the individual effects of ischemia and reperfusion, we generated 2-DE gels from rabbit myocardium subjected to brief ischemia alone (15I/0R), and observed alterations of 33 protein spots, including 18/20 seen in both 15I/60R-treated and 15I/60R + MPG-treated tissue. The tissue was also subjected to ischemia in the presence of MPG (15I/0R + MPG), and 21 spot changes, representing 14 protein variants, remained altered despite the presence of the OFR scavenger. These ischemia-specific proteins comprised those involved in energy metabolism (lactate dehydrogenase and ATP synthase alpha), redox regulation (NADH ubiquinone oxidoreductase 51 kDa and GST Mu), and stress response (Hsp27 and 70, and deamidated alpha B-crystallin). We conclude that contractile dysfunction associated with myocardial stunning is predominantly caused by OFR damage at the onset of reperfusion, but that OFR-independent damage also occurs during ischemia. These ischemia-specific protein modifications may be indicative of early myocardial injury.     

Is acidosis the clue to the loss of structure and functioning of the sarcolemma?

The only way for a tissue or organ to survive ischemia is by reperfusion or restoration of the blood flow. However, if the ischemic period is too long reperfusion leads to a Ca2+ overload of the myocardial cells and thereby to cell death. The question is; what are the key events during ischemia which cause this transition from reversible to irreversible injury. In this article we discuss whether acidosis may play a crucial role by inducing Ca2+ release from the sarcolemma and reorganization of membrane components especially the membrane lipids, i.e. lateral phase separation, resulting in membrane protein clustering and changes in lipid asymmetry.     

Detection of regional temporal abnormalities in left ventricular function during acute myocardial ischemia

Echocardiographic diagnosis of myocardial ischemia is based on visualizing hypokinesis, which occurs late in the ischemic cascade. We hypothesized that temporal changes in endocardial motion may constitute sensitive early markers of ischemia. Two protocols were performed in 19 anesthetized pigs. Protocol 1 included 54 intracoronary balloon occlusions. Transthoracic images were acquired at baseline and every 15 s during 5 min of occlusion and reperfusion. In protocol 2, ischemia was induced in 12 animals by use of graded dobutamine infusion, after creating significant partial occlusions without a resting wall motion abnormality. Systolic and diastolic endocardial motion was color encoded using color kinesis and analyzed using custom software. All ischemic episodes caused detectable and reversible changes. The earliest sign of ischemia was tardokinesis in 31/54 occlusions, whereas hypokinesis appeared first in 23/54 cases. Dobutamine-induced ischemia caused tardokinesis first in 9/12 and hypokinesis in 3/12 animals. Reversible ischemic changes in regional left ventricular performance can be objectively detected using analysis of echocardiographic images and will likely improve the early noninvasive diagnosis of acute ischemia.     

Postischemic injury in isolated rat hearts is not aggravated by prior depletion of myocardial glutathione

The aim of this study was to test the hypothesis that a decreased myocardial concentration of reduced glutathione (GSH) during ischemia renders the myocardium more susceptible to injury by reactive oxygen species generated during early reperfusion. To this end, rats were pretreated with L-buthionine-S,R-sulfoximine (2 mmol/kg), which depleted myocardial GSH by 55%. Isolated buffer-perfused hearts were subjected to 30 min of either hypothermic or normothermic no-flow ischemia followed by reperfusion. Prior depletion of myocardial GSH did not lead to oxidative stress during reperfusion, as myocardial concentration of glutathione disulfide (GSSG) was not increased after 5 and 30 min of reperfusion. In addition, prior depletion of GSH did not exacerbate myocardial enzyme release, nor did it impair the recoveries of tissue ATP, coronary flow rate and left ventricular developed pressure during reperfusion after either hypothermic or normothermic ischemia. Even administration of the prooxidant cumene hydroperoxide (20 M) to postischemic GSH-depleted hearts during the first 10 min of reperfusion did not aggravate postischemic injury, although this prooxidant load induced oxidative stress, as indicated by an increased myocardial concentration of GSSG. These results do not support the hypothesis that a reduced myocardial concentration of GSH during ischemia increases the susceptibility to injury mediated by reactive oxygen species generated during reperfusion. Apparently, myocardial tissue possesses a large excess of GSH compared to the quantity of reactive oxygen species generated upon reperfusion. (Mol Cell Biochem 156: 79-85, 1996)     

Coupling of angiotensin II AT1 receptors to neuronal NHE activity and carrier-mediated norepinephrine release in myocardial ischemia

In ischemia, cardiac sympathetic nerve endings (cSNE) release excessive amounts of norepinephrine (NE) via the nonexocytotic Na(+)-dependent NE transporter (NET). NET, normally responsible for NE reuptake into cSNE, reverses in myocardial ischemia, releasing pathological amounts of NE. This carrier-mediated NE release can be triggered by elevated intracellular Na(+) levels in the axoplasm. The fact that ischemia activates the intracellular pH regulatory Na(+)/H(+) exchanger (NHE) in cSNE is pivotal in increasing intraneuronal Na(+) and thus activating carrier-mediated NE release. Angiotensin (ANG) II levels are also significantly elevated in the ischemic heart. However, the effects of ANG II on cSNE, which express the ANG II receptor, AT(1)R, are poorly understood. We hypothesized that ANG II-induced AT(1)R activation in cSNE may be positively coupled to NHE activity and thereby facilitate the pathological release of NE associated with myocardial ischemia. We tested this hypothesis in a cSNE model, human neuroblastoma cells stably transfected with rat recombinant AT(1A) receptor (SH-SY5Y-AT(1A)). SH-SY5Y-AT(1A) constitutively expresses amiloride-sensitive NHE and the NET. NHE activity was assayed in BCECF-loaded SH-SY5Y-AT(1A) as the rate of the Na(+)-dependent alkalinization in response to an acute acidosis. ANG II activation of AT(1)R markedly increased NHE activity in SH-SY5Y-AT(1A) via a Ca(2+)-dependent pathway and promoted carrier-mediated NE release. In addition, in guinea pig cSNE expressing native AT(1)R, ANG II elicited carrier-mediated NE release. In SH-SY5Y-AT(1A) and cSNE, amiloride inhibited the ANG II-mediated release of NE. Our results provide a link between AT(1)R and NHE in cSNE, which can exacerbate carrier-mediated NE release during protracted myocardial ischemia.     

Ascorbyl free radical as a reliable indicator of free-radical-mediated myocardial ischemic and post-ischemic injury. A real-time continuous-flow ESR study

The real-time kinetics of the release of ascorbyl free radicals in the coronary perfusate from isolated rat hearts submitted to an ischemia/reperfusion sequence has been achieved by continuous-flow ESR using high-speed acquisition techniques. Enhanced ESR detection of ascorbyl free radicals was obtained by addition of dimethyl sulfoxide (Me2SO), a strong cation chelator and oxidizing agent. A continuous-flow device allowed a direct monitoring of the ascorbyl free radical and/or ascorbate leakage in coronary perfusate by observation of the ascorbyl radical doublet (aH = 0.188 mT and g = 2.0054). 1. The results showed that ascorbyl free radical release occurred mainly during sequences of low-flow ischemia (90 min) coupled or not with 30 min of zero-flow ischemia followed by reperfusion (60 min). The kinetic profiles of ascorbyl-free-radical detection confirm in quantitative terms the expected correlation between the duration of the ischemic insult and the magnitude of ascorbate extracellular release upon reperfusion. There is indication that ascorbyl free radical depletion could be secondary to oxygen-derived-free-radical-induced cellular damage. 2. The amount of residual ascorbic acid was quantitated on myocardial tissue at the end of reperfusion using Me2SO as extracting solvent. Intense oxidation of ascorbate and chemical stabilization of the resulting free radical species provided by Me2SO allowed ESR measurement of a marked tissue ascorbate depletion related to the duration of ischemia. 3. Perfusion of superoxide dismutase during low-flow ischemia and the first 10 min of reperfusion greatly inhibited both extracellular release and endogenous ascorbate depletion. These results suggest that the ascorbate redox system constitutes a major protective mechanism against free-radical-induced myocardial injury. 4. The proposed direct ESR detection of ascorbyl free radicals in the coronary perfusates or in tissue extracts does not require extensive chemical preparation and conditioning of effluent or tissue samples. It provides an interesting straightforward alternative to the evaluation of detrimental free radical processes affecting the myocardium during ischemia and reperfusion.     

Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning

Ischemic preconditioning is known to protect the myocardium from ischemia-reperfusion injury. We examined the transmural release of bradykinin during myocardial ischemia and the influence of ischemic preconditioning on bradykinin release during subsequent myocardial ischemia. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery in anesthetized cats. Cardiac microdialysis was performed by implantation and perfusion of dialysis probes in the epicardium and endocardium. In eight animals, bradykinin release was greater in the endocardium than in the epicardium (14.4 +/- 2.8 vs. 7.3 +/- 1.7 ng/ml, P < 0.05) during 30 min of ischemia. In seven animals subjected to preconditioning, myocardial bradykinin release was potentiated significantly from 2.4 +/- 0.6 ng/ml during the control period to 23.1 +/- 2.5 ng/ml during 30 min of myocardial ischemia compared with the non-preconditioning group (from 2.7 +/- 0.6 to 13.4 +/- 1.9 ng/ml, P < 0.05, n = 6). Thus this study provides further evidence that transmural gradients of bradykinin are produced during ischemia. The results also suggest that ischemic preconditioning enhances bradykinin release in the myocardial interstitial fluid during subsequent ischemia, which is likely one of the mechanisms of cardioprotection of ischemic preconditioning.     

Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release

Although electrical vagal stimulation exerts beneficial effects on the ischemic heart such as an antiarrhythmic effect, whether it modulates norepinephrine (NE) and acetylcholine (ACh) releases in the ischemic myocardium remains unknown. To clarify the neural modulation in the ischemic region during vagal stimulation, we examined ischemia-induced NE and ACh releases in anesthetized and vagotomized cats. In a control group (VX, n = 8), occlusion of the left anterior descending coronary artery increased myocardial interstitial NE level from 0.46+/-0.09 to 83.2+/-17.6 nM at 30-45 min of ischemia (mean+/-SE). Vagal stimulation at 5 Hz (VS, n = 8) decreased heart rate by approximately 80 beats/min during the ischemic period and suppressed the NE release to 24.4+/-10.6 nM (P < 0.05 from the VX group). Fixed-rate ventricular pacing (VSP, n=8) abolished this vagally mediated suppression of ischemia-induced NE release. The vagal stimulation augmented ischemia-induced ACh release at 0-15 min of ischemia (VX: 11.1+/-2.1 vs. VS: 20.7+/-3.9 nM, P < 0.05). In the VSP group, the ACh release was not augmented. In conclusion, vagal stimulation suppressed the ischemia-induced NE release and augmented the initial increase in the ACh level. These modulations of NE and ACh levels in the ischemic myocardium may contribute to the beneficial effects of vagal stimulation on the heart during acute myocardial ischemia.     

An approach to determine myocardial ischemia by hidden Markov models

A hidden Markov model (HMM) of electrocardiogram (ECG) signal is presented for detection of myocardial ischemia. The time domain signals that are recorded by the ECG before and during the episode of local ischemia were pre-processed to produce input sequences, which is needed for the model training. The model is also verified by test data, and the results show that the models have certain function for the detection of myocardial ischemia. The algorithm based on HMM provides a possible approach for the timely, rapid and automatic diagnosis of myocardial ischemia, and also can be used in portable medical diagnostic equipment in the future.     

An approach to determine myocardial ischemia by hidden Markov models

A hidden Markov model (HMM) of electrocardiogram (ECG) signal is presented for detection of myocardial ischemia. The time domain signals that are recorded by the ECG before and during the episode of local ischemia were pre-processed to produce input sequences, which is needed for the model training. The model is also verified by test data, and the results show that the models have certain function for the detection of myocardial ischemia. The algorithm based on HMM provides a possible approach for the timely, rapid and automatic diagnosis of myocardial ischemia, and also can be used in portable medical diagnostic equipment in the future.     

Ischemia stimulates the release of atrial natriuretic peptide from rat cardiac ventricular myocardium in vitro.

The effect of ischemia on atrial natriuretic peptide (ANP) release from heart ventricles was studied by exposing the perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats to global ischemia after excision of the atria. Ischemia for 2, 5 and 20 min caused an increase of 0.3 +/- 1.1, 12.4 +/- 5.5 and 11.4 +/- 4.2 ng/g dry weight in ANP release of the WKY ventricles, respectively. ANP release increased 3.4 +/- 2.8 ng/g dry weight after 5 minutes' ischemia from the SHR ventricles. The increase was not caused by cell damage, as only processed form of the peptide was detected in the perfusates. The increase in ANP release in the WKY ventricles correlated positively with the tissue lactate/pyruvate ratio (r = 0.85) and adenosine (r = 0.99), and negatively with the phosphorylation potential (r = -0.70). The results indicate that ventricular ischemia increases ANP release, probably due to changes in myocardial energy metabolism.     

Non-linear dynamic analysis of the cardiac rhythm during transient myocardial ischemia.

Coronary artery occlusions related to myocardial ischemia drive cardiac control system reactions that may lead to heart failure. The purpose of this study was to assess the autonomic nervous system (ANS) response during prolonged percutaneous transluminal coronary angioplasty (PTCA). Continuous ECG data were acquired from 50 patients before and during PTCA, with occlusions in the left anterior descending, left circumflex or right coronary artery. Heart rate variability (HRV) was analyzed for 3-min segments of the R-R interval signal obtained from ECG data. The ANS behavior was evaluated by HRV analysis using fractal-like indices. The fractal scalar exponent alpha(1) and power-law slope beta decreased considerably during PTCA. This indicates that significant reactions of autonomic control of the heart rate occurred during coronary artery occlusions, with a reduction in complexity of the ANS.     

Relation between energy metabolism,glycolysis, noradrenaline release and duration of ischemia

We studied the effect of 12–36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = –0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline lOx (p < 0.05) . Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x and 200x (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r =–0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.     

Expression of VEGF and angiopoietins-1 and -2 during ischemia-induced coronary angiogenesis

The mechanisms underlying coronary capillary growth in response to ischemia are undefined. We hypothesized that the expression of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)/Tie-2 were involved in capillary growth as an adaptation to ischemia. To test this hypothesis we measured capillary density, and the expressions of VEGF, Ang-1, Ang-2, and the Tie-2 receptor and its phosphorylation state during repetitive episodes of myocardial ischemia in chronically instrumented canines. Repetitive episodes of ischemia were induced by multiple (once/hour; 8/day), brief (2 min) occlusions of the left anterior descending coronary artery for 1, 7, 14, or 21 days. A sham group received the same instrumentation as the experimental groups but not the occlusion protocol. Collateral blood flow (microspheres) progressively increased from 9 +/- 3 to 83 +/- 10 ml. min-1. 100 g-1 on day 21. Capillary density increased at day 7 from 2378 +/- 53 (sham) to 2962 +/- 60/mm2, but it decreased to 2594 +/- 39/mm2 at day 21. Both VEGF and Ang-2 expression in myocardial interstitial fluid (Western analyses) peaked at day 3 of the repetitive occlusions but waned thereafter. In contrast the expression of Ang-1 remained relatively constant at all times in the occlusion groups. In shams, the expression of VEGF and Ang-2 was low and constant at all times. Tie-2 phosphorylation myocardial decreased decreased at day 7 but increased at 21 days of occlusions (P < 0.05). Our results indicate that capillary density was augmented by myocardial ischemia, but after development of collaterals and restoration of flow to the ischemic zone, capillary density returned to control levels. The change in capillary density paralleled with VEGF and Ang-2 expression but was inversely related to Tie-2 phosphorylation. We speculate the coronary angiogenesis is a coordinated event involving the expression of both VEGF and Ang-2 and that therapeutic angiogenic strategies may ultimately require treatment with more than a single factor.     

Release of norepinephrine from the rat ovary: local modulation of gonadotropins.

Experiments were undertaken to define the role of gonadotropins in the release of norepinephrine and the relationship with beta-receptors of the ovary. Rat ovaries were removed at different stages of the estrous cycle and incubated in [3H]norepinephrine. Subsequently, ovaries were electrically stimulated and the release of [3H]norepinephrine was recorded. There were no changes in the norepinephrine content during the estrous cycle. The ovary exhibited cyclical variation in norepinephrine-induced release during the estrous cycle. The lowest release of norepinephrine was found during diestrus; there was an increase during proestrus and estrus followed by a decline during metestrus. The release of norepinephrine changed in the opposite way to the beta-receptor number, suggesting a process involving down-regulation between norepinephrine release and beta-receptors of the ovary. Norepinephrine released from the ovary was locally regulated by gonadotropins. The presence of FSH in the superfusion medium stimulated the norepinephrine-induced release from the ovaries of rats in diestrus (by 20%) and estrus (by 40%), but no effect was found during proestrus. In addition, the presence of hCG stimulated (by 40%) norepinephrine-induced release during proestrus, but no changes were apparent during the other stages of the estrous cycle. These results suggest that the local action of gonadotropins on nerve terminals of the ovary might be one of the factors governing the changes in norepinephrine release through the estrous cycle. The changes in the norepinephrine released to the synaptic cleft might exert down-regulation on the beta-adrenergic receptor content of the ovary and in this way control the ovarian steroid secretory activity.     

A comprehensive approach to visual and functional assessment of experimental vascular lesions in vivo

The role of metabolic factors derived from cardiac muscle in the development of reactive hyperemia after brief occlusions of the coronary circulation seems to be well established. However, the contribution of occlusion-induced changes in hemodynamic forces to eliciting reactive hyperemia is less known. We hypothesized that in isolated coronary arterioles changes in intraluminal pressure and flow, during and after release of occlusion (O/R), themselves via activating intrinsic mechanosensitive mechanisms, elicit release of vasoactive factors resulting in reactive dilations. Thus in isolated coronary arterioles (diameter: 88 +/- 8 microm) changes in diameter to changes in pressure or pressure plus flow (P+F) during and after a brief period (30, 60, and 120 s) of O/R of cannulating tube were measured by videomicroscopy. In response to both types of O/R, diameter first decreased, then, subsequently increased during occlusions. When only pressure was changed (from 80-10-80 mmHg), after release of occlusion, peak dilations increased as a function of the duration of occlusions. After flow was established (30 microl/min), O/R elicited changes in both pressure and flow (from 80-10-80 mmHg and from 0 to 30 microl/min). In these conditions, after the release of occlusions, not only the peak but also the duration of reactive dilation increased significantly as a function of the length of occlusions. The dilations during, and peak dilations after occlusions both in pressure and P+F protocols were significantly reduced by the inhibition of NO synthase with Nomega-nitro-L-arginine-methyl-ester (L-NAME) or by endothelium removal, whereas duration of postocclusion dilations were reduced by L-NAME or by endothelium removal only in P+F protocols. Furthermore, in both protocols, catalase significantly reduced the peak but not the duration of reactive dilations. Thus, mechanosensitive mechanisms that are sensitive to deformation, pressure, stretch, and wall shear stress elicit release of NO and H2O2, resulting in reactive dilation of isolated coronary arterioles.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.