Distribution Of Myocardial Blood Flow Research Articles

Rapid ventricular pacing induces delayed cardioprotection against myocardial stunning

Tachycardia with rapid ventricular pacing induces delayed preconditioning against arrhythmias secondary to coronary artery occlusion (CAO) and reperfusion (CAR) but its effects on myocardial stunning remains unknown. Accordingly, we investigated whether delayed preconditioning with ventricular pacing develops against myocardial stunning and whether this phenomenon is triggered by reactive oxygen species. Eight chronically instrumented conscious dogs underwent three experimental sequences in a random order a week apart: (a) 10-min CAO (coronary occluder) followed by CAR, i.e. “Control” sequence; (b) pacing (right ventricular electrodes, 240 beats/min during 40 min) performed 24 h before the 10-min CAO, i.e. “PC” sequence; and (c) N-(2-mercaptopropionyl)-glycine (MPG, 100 mg/kg per h) administered concomitantly to pacing and 10-min CAO performed 24 h later, i.e. “PC + MPG” sequence. During “Control”, left ventricular (LV) wall thickening (%, sonomicrometry) was dramatically reduced during CAO (–96 ± 5% from 2.9 ± 0.4 mm) and remained depressed during CAR demonstrating myocardial stunning. During “PC”, LV wall thickening was not altered by pacing per se and was similarly decreased during CAO vs. “Control”. However, during CAR, LV wall thickening was improved vs. “Control” (e.g. –24 ± 5% and –8 ± 4% from corresponding baseline for “PC” and “Control”, respectively at 2 h-CAR; P < 0.05), demonstrating delayed preconditioning. Administration of MPG during pacing ( n = 5) abolished the beneficial effects of pacing. Myocardial lactate extraction and transmural distribution of regional myocardial blood flow (fluorescent microspheres) were not modified, by pacing. In conclusion, tachycardia with rapid ventricular pacing induces delayed cardioprotection against myocardial stunning. The production of reactive oxygen species independently from ischemia appears to be a major trigger for this phenomenon.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Myocardial Contrast Echocardiography in the Assessment of Patients With Chronic Coronary Artery Disease

The development of new contrast agents and new imaging methods has lead to an emerging field of applications for myocardial contrast echocardiography (MCE) in patients suffering from chronic ischemic heart disease. Echo contrast allows the assessment of myocardial perfusion (MP) by imaging the coronary microcirculation. Several echocardiographic modalities are available, the main difference between them being the acoustic power needed to perform the study. MP is evaluated by assessing the changes in myocardial videointensity that occur after intravenous contrast injection. Evaluation of these patients is performed by using different techniques. Evaluation of coronary stenosis may be performed by using stress tests or without its use. Coronary artery stenosis > 50% of the coronary luminal diameter reveals a decreased hyperemic response when myocardial oxygen demand is increased. Different methods to evaluate the presence of relevant coronary stenosis have been developed: evaluation of myocardial blood flow reserve, evaluation of myocardial blood volume, and evaluation of the transmural distribution of myocardial blood flow. The combination of wall motion analysis with MCE assessment has been demonstrated to achieve the best balance between sensitivity (86%) and specificity (88%), with the highest accuracy (86%). Without the need of any stress, the ratio systolic/diastolic myocardial blood volume has been described to increase with the presence of a epicardial coronary stenosis and it may be measured by MCE. Myocardial viability is also one of the potentials of MCE. Microvascular integrity, demonstrated by MCE, is an indicator of preserved viability and predicts functional recovery that has been validated in the setting of chronic left ventricular dysfunction secondary to chronic coronary artery disease and in the setting of post acute myocardial infarction left ventricular dysfunction. contrast echocardiography provides an interesting tool that offers the potential of a complete evaluation of patients with chronic coronary artery disease. This includes both diagnostic and prognostic evaluation.

Cardiac Positron Emission Tomography

Positron emission tomography (PET) is a non-invasive radionuclide imaging technique that, when used with appropriate radiotracers and kinetic models, permits absolute quantitative measurements of myocardial perfusion, metabolism and receptor densityin vivo. Assessment of the coronary vasodilator reserve (ratio of hyperaemic to baseline myocardial blood flow) has provided insights into both the functional significance of coronary artery stenoses in patients with coronary artery disease and abnormalities of the coronary microcirculation in patients with different cardiomyopathies. The use of PET to identify myocardial viability (by preserved uptake of ¹⁸F-fluoro-deoxy-glucose) allows the localisation of hibernating myocardium and the quantification of infarct size in patients with coronary artery disease. Measurements of myocardial oxygen consumption using PET with oxygen-15 and ¹¹C-acetate have provided information on myocardial metabolism during ischaemia and myocardial stunning. Tracers and kinetic models have also been developed permitting investigation of the role of the cardiac autonomic nervous system in the pathophysiology of heart failure and arrhythmogenesis. The high spatial resolution of modern PET cameras and the validation of new tracers may provide further insights into cardiac pathophysiology, e.g. to assess the transmural distribution of myocardial blood flow and metabolism across the left ventricular wall.

Relation between local myocardial growth and blood flow during chronic ventricular pacing.

Several studies have shown that, per unit mass, myocardial blood flow (MBF) and oxygen consumption are similar in hypertrophic and non-hypertrophic ventricles. This observation may be explained by the degree of myocardial growth matching the increase in oxygen demand. Such matching may, however, not be perfect at the local level, because substantial heterogeneity of MBF exists within the ventricular wall. We investigated to what extent local growth and MBF are matched after redistribution of workload within the left ventricular (LV) wall. Redistribution of workload was established by ventricular pacing at physiological heart rate, which induces asynchronous activation and contraction. Local wall mass (2D-echocardiography) and MBF (fluorescent microspheres) were determined in the canine LV wall before (t=0) and after 6 months of normal sinus rhythm (SHAM group, n=5) or 6 months of pacing at the LV free wall (PACE group, n=8). During acute pacing MBF (ml/min/g) increased with increasing distance to the pacing site. Local relative MBF (rMBF, local MBF normalized to mean MBF in the LV wall) varied from 0.8 adjacent to the pacing site to 1.2 in remote regions. After 6 months of pacing these regional differences had disappeared, probably due to changes in wall mass, which increased with increasing distance to the pacing site (by up to 39+/-13%). In SHAM animals rMBF at t=0 correlated well with rMBF 6 months later (r=0.71). In PACE animals, however, this correlation was poor (r=0.33), because rMBF increased in regions close to the pacing site with initial rMBF<1 and rMBF decreased in regions remote from the pacing site with initial rMBF>1. After redistribution of workload within the LV wall as induced by ventricular pacing, local load-regulated growth tends to equalize MBF distribution, but local adaptation of MBF also depends on initial MBF.

Myocardial blood flow after chronic cardiac decentralization in anesthetized dogs: effects of ACE-inhibition

Coronary blood flow regulation was studied in dogs with an intact or chronically decentralized intrinsic cardiac nervous system. We also examined the effect of angiotensin-converting enzyme inhibition (ACEI) on coronary autoregulatory pressure–flow relations and distribution of blood flow since the renin–angiotensin system may play a critical role in vasoregulation. Myocardial oxygen demand was reduced in the chronic decentralized dogs compared to the control dogs. The lower pressure limit of the autoregulatory pressure–flow relation was similar for the control and chronic decentralized dogs (47±2 and 44±7 mm Hg, respectively; p=NS). After ACEI, the lower pressure limit shifted leftward to 40 mm Hg ( p=0.001) in both groups. Concomitant blockade of cyclooxygenase, bradykinin catabolism and nitric oxide synthase had no further effect on the lower pressure limit. Total myocardial blood flow was lower ( p=0.001) in the chronic decentralized dogs compared to the control dogs, while transmural distribution of blood flow was preserved in both groups. The results show that even though myocardial oxygen requirements are lower in the chronically decentralized heart compared to controls, coronary autoregulation is maintained at levels observed in normally innervated hearts. The present findings indicate that intrinsic cardiac neurons contribute to coronary autoregulatory control and myocardial blood flow distribution even in the absence of cardiac connections to the central nervous system. In addition, in the chronic decentralized dog, ACEI allows the heart to work at lower coronary perfusion pressures while myocardial blood flow distribution is preserved.

Effect of estrogen replacement therapy on distribution of myocardial blood flow in female anesthetized rabbits.

Estrogen replacement therapy reduces risk of cardiovascular events by altering coronary vasoregulation and distribution of blood flow. Vessel reactivity and blood flow distribution were assessed in anesthetized female rabbits in the following groups: 1) sham, 2) ovariectomy, 3) ovariectomy + 17beta-estradiol, and 4) ovariectomy + dehydroepiandrosterone. After a 2-wk treatment, cardiac hemodynamics, vascular reserve, and blood flow were evaluated during the following infusions: 1) NaCl, or vehicle (0.5 ml/min), 2) acetylcholine (2 mg/kg), 3) isoproterenol (2 mg. kg(-1). min(-1)), and 4) chromonar (8 mg/kg). In hearts from ovariectomized rabbits, autoregulatory blood flow was preserved despite lower diastolic perfusion pressures (55 +/- 8 vs. 64 +/- 8 mmHg in sham) and rate-pressure product (14.4 +/- 0.8 vs. 19.3 +/- 0.8 beats/min. mmHg x 10(-3)). Estrogen replacement therapy restored coronary pressure and reserve, and all drugs increased vascular conductance. In conclusion, in hearts from ovariectomized rabbits, vascular reserve declined because coronary pressure was lower; however, blood flow was preserved at a higher level than expected for oxygen demand. Estrogen replacement therapy restores myocardial oxygen supply-demand indices and returns coronary pressure-flow data to levels observed in animals with intact ovaries.

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia

Objectives. Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). Methods. In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure–volume loops. SCS was accomplished by stimulating the dorsal T1–T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. Results. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure–volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. Conclusions. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure–volume dynamics in the anesthetized experimental preparation.

Is chronically dysfunctional yet viable myocardium distal to a severe coronary stenosis hypoperfused?

Background. Controversy exists regarding the perfusion status of chronically dysfunctional yet viable myocardium. Studies investigating the pathophysiology of this condition have reached different conclusions, with some suggesting that myocardial blood flow (MBF) in these regions is normal at rest with regional dysfunction resulting from repetitive stress-induced ischemia (stunned myocardium), whereas others have proposed that MBF is chronically reduced at rest (hibernating myocardium). However, adequately powered experimental studies investigating this question in an appropriate animal model using clinically available techniques have not been performed. Based on the mixed results of prior studies, we hypothesized that these chronically dysfunctional yet viable regions may actually represent a mixture of hibernation and stunning. Consequently, the purpose of this study was to quantitatively determine the distribution of MBF in left ventricular regions with chronically impaired resting function but preserved viability in a large population of animals with single-vessel coronary stenosis in an attempt to further elucidate the mechanism(s) responsible for chronic, reversible myocardial dysfunction. Methods. Fifty-two adult mini-swine with 90% proximal left circumflex (LCx) stenosis underwent dynamic positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose and dobutamine stress echocardiography (DSE) (5 to 40 μg/kg/min) 1 month after stenosis creation. Values of MBF and FDG uptake by PET and wall motion score index (WMSI) by DSE were compared using a standard 16-segment model. Results. Of 312 possible LCx segments seen on PET, 303 (97.1%) were visualized by DSE. Of the 303 LCx segments, 279 (92.1%) had rest dysfunction (WMSI ≥ 2) by DSE. One hundred eighty-two segments (60.1%) had decreased (< 85% reference) MBF at rest with preserved to increased (> 60% reference) FDG uptake and were classified as hibernating. Ninety-two segments (30.4%) had preserved MBF (≥ 85% reference) and were classified as stunned. Five segments (1.7%) with reduced (≤ 60% reference) FDG uptake by PET and akinesis or dyskinesis at rest (WMSI ≥ 3) and no contractile reserve were considered infarcted. Hibernating segments had significantly higher FDG uptake at rest (360.7 ± 48.3 vs 212.3 ± 17.7% septal values; p < 0.001) than stunned segments consistent with greater resting ischemia. Likewise, mean rest WMSI was also worse in hibernating versus stunned segments (2.35 ± 0.04 vs 2.13 ± 0.04; p < 0.001). There was no difference in the percentage of hibernating versus stunned segments exhibiting contractile reserve during dobutamine infusion (55.5 vs 63.7%; p = 0.4), indicating similar degrees of viability. Conclusions. Myocardial hibernation and stunning appear to frequently coexist in regions served by a stenotic coronary vessel. Hibernating regions appear to have greater resting ischemia based on higher values of FDG uptake and greater resting dysfunction. Reversible left ventricular dysfunction in the setting of chronic coronary artery disease is likely due to a combination of these two mechanisms.

Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia.

On the hypothesis that coronary sinus occlusion (CSO) may reduce myocardial ischemia, we examined the effects of CSO on coronary collateral blood flow and on the distribution of regional myocardial blood flow (RMBF) in dogs. Thirty-eight anesthetized dogs underwent occlusion of the left anterior descending coronary artery with or without CSO and intact vasomotor tone. We measured RMBF and intramyocardial pressure (IMP) in the subendocardium (Endo) and subepicardium (Epi) separately. With intact vasomotor tone, CSO during ischemia significantly increased RMBF in the ischemic region (IR), particularly in Endo from 0.17 +/- 0.03 to 0.33 +/- 0.05 ml x min(-1) x g(-1) (P < 0.05), and increased the Endo/Epi from 0.59 +/- 0.10 to 1.15 +/- 0.15 (P < 0.01). These effects of CSO were partially abolished by adenosine. However, the Endo/Epi was still increased from 0.90 +/- 0.13 to 2.09 +/- 0.30 (P < 0.01). The changes in RMBF in IR were significantly correlated with the peak CS pressure during CSO. The Endo/Epi of IMP in IR was significantly decreased during CSO. In conclusion, CSO potentially enhances coronary collateral flow, and preserves the ischemic myocardium, especially in Endo.

Preliminary report on high thoracic epidural analgesia: Relationship between its therapeutic effects and myocardial blood flow as assessed by stress thallium distribution

Objectives: To extend the duration of high thoracic epidural analgesia (HTEA) treatment compared with the authors' previous studies, to test the hypothesis that the mechanism by which HTEA reduces angina during long-term treatment includes an improvement in myocardial blood flow distribution and a reduction in stress-induced ischemia, and to show that new myocardial infarctions are not masked or missed in patients receiving HTEA. Design: Prospective consecutive study. Setting: Department of Veteran's Affairs medical center and university-affiliated hospital. Participants: Six consenting adult patients. Interventions: Patients were evaluated before HTEA catheter insertion and >2 months after HTEA catheter insertion with stress thallium tests. Measurements and Main Results: Two of 6 patients had improvement but not resolution of stress-induced ischemia at 8 and 12 months. The remaining 4 patients had no change in stress-induced ischemia. None of the 6 patients had any new areas of ischemia or infarction as determined by stress thallium tests. Conclusions: The authors previously showed that HTEA is safe and effective in relieving refractory angina pectoris. The current study shows that this therapeutic effect persists and does not appear to be related to a change in myocardial blood flow; rather the improvement in symptoms probably results, in part, from an anesthetic effect. HTEA does not mask the development of new myocardial infarctions. Copyright © 2000 by W.B. Saunders Company

Platelet GPIIb/IIIa receptor blockade reduces infarct size in a canine model of ischemia-reperfusion

OBJECTIVESWe studied the effects of N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate (MK-0852) (platelet GPIIb/IIIa receptor blocker) on peak reactive hyperemia, distribution of blood flow, regional contractile function and infarct size in a canine model of acute ischemia-reperfusion injury.BACKGROUNDPlatelet activation and formation of platelet microaggregates in coronary vessels could contribute to ischemia-induced myocyte injury. Inhibition of platelet aggregation could reduce ischemia-reperfusion injury.METHODSThree groups of dogs (n = 10/group) were studied; group 1—heparin (HEP) (100 U/kg/h intravenously), group 2—MK-0852 (300 μg/kg intravenous bolus followed by 3 μg/kg/min for 3 h) and group 3—MK-0852 plus HEP. Infarct size after 60 min regional ischemia and 3 h reperfusion was evaluated by tetrazolium staining and normalized to risk area (Monastral blue dye).RESULTSInfarct size in HEP-treated controls was 32.4 ± 2.8%; in MK-0852 without or with HEP groups, infarct size was 17.4 ± 1.9% (p = 0.001) and 23.4 ± 3.0% (p = 0.04), respectively. Cardiac hemodynamics and rate-pressure product were comparable between groups. Multivariate analysis using collateral blood flow as the independent variable confirmed the cytoprotective actions of MK-0852. Postischemic peak reactive hyperemia in the infarct-related artery was depressed in all groups; during reperfusion, transmural distribution of myocardial blood flow returned to near control levels, but severe regional hypokinesia persisted.CONCLUSIONSDiminished infarct size with MK-0852 treatment suggests an additional mechanism of benefit for GPIIb/IIIa blockers beyond stabilization of a “culprit” acute coronary lesion. This cytoprotective effect was unrelated to preservation of coronary vasoreactivity (assessed by reactive hyperemia), restoration of blood flow across the myocardium or acute improvement in contractility.

Effect of angiotensin inhibition on the coronary artery lower pressure limit in anesthetized dogs

The renin-angiotensin system plays a critical role in regulating vasoconstriction and vasodilatation that can influence myocardial blood flow and its transmural distribution. We tested the hypothesis that angiotensin inhibition can induce a leftward shift of the coronary autoregulatory pressure-flow relation and preserve distribution of myocardial blood flow at lower coronary perfusion pressures. We established circumflex artery pressure-flow relations under baseline conditions and after intracoronary enalaprilat or losartan potassium. Thereafter, transmural myocardial blood flow was measured at baseline and at the lower coronary pressure limit (LPL). With enalaprilat, the LPL was shifted leftward from 48 +/- 6 mmHg at baseline to 43 +/- 3 mmHg (P = 0.026); with losartan, the LPL was shifted leftward from 48 +/- 10 mmHg at baseline to 41 +/- 5 mmHg (P = 0.027). The leftward shift occurred while cardiac hemodynamics and MVO2 were maintained at control levels. These results indicate that angiotensin inhibition extends the range of coronary autoregulation to lower LPL while preserving myocardial blood flow distribution, a physiologic effect that might explain the lower incidence of coronary events in treated patients.

Altered myocardial microvascular 3D architecture in experimental hypercholesterolemia.

Experimental hypercholesterolemia (HC) impairs intramyocardial microvascular function. However, whether this is associated with alterations in microvascular architecture remained unknown. Using a novel 3D micro-CT scanner, we tested the hypothesis that HC is associated with an alteration in the microvascular architecture. Pigs were euthanized after 12 weeks of either normal (n=6) or 2% HC (n=6) diet. The hearts were excised and the coronary arteries injected with a radiopaque contrast material. Myocardial samples were scanned with micro-CT, and 3D images were reconstructed with 21-microm cubic voxels. The myocardium was tomographically subdivided into subepicardium and subendocardium, and microvessels (<500 microm in diameter) were counted in situ within each region. In the subendocardium of HC pigs, the intramyocardial density of microvessels was significantly higher than in normal animals (1221.4+/-199.7 versus 758.3+/-90.8 vessels/cm(3), P:<0.05) because of an increase in the number of microvessels <200 microm in diameter (1214.4+/-199.7 versus 746. 6+/-101.5 vessels/cm(3), P:<0.05). The subepicardial vascular density was similar in both groups. -HC has differential effects on the spatial density of the subendocardial microvasculature that may play a role in regulation and/or spatial distribution of myocardial blood flow. This study also demonstrates the feasibility of studying myocardial microvascular architecture with micro-CT in pathophysiological states.

Effects of primary resuscitation from shock on distribution of myocardial blood flow.

Hemorrhagic shock alters heterogeneity of regional myocardial perfusion (RMP) in the presence of critical coronary stenosis in pigs. Conventional resuscitation has failed to reverse these effects. We hypothesized that improvement of the resuscitation regime would lead to restoration of RMP heterogeneity. Diaspirin-cross-linked hemoglobin (10 g/dl; DCLHb) and human serum albumin (8.0 g/dl; HSA) were used. After baseline, a branch of the left coronary artery was stenosed; thereafter, hemorrhagic shock was induced. Resuscitation was performed with either DCLHb or HSA. At baseline, the fractcal dimension (D) of subendocardial myocardium was 1.31 +/- 0.083 (HSA) and 1.35 +/- 0.106 (DCLHb) (mean +/- SD). Coronary stenosis increased subendocardial D slightly but consistently only in the DCLHb group (1.39 +/- 0.104; P < 0.05). Shock reduced subendocardial D: 1.21 +/- 0.093 (HSA; P = 0.10), 1.25 +/- 0.092 (DCLHb; P < 0.05). Administration of DCLHb increased subendocardial D in 7 of 10 animals (1.31 +/- 0.097; P = 0.066). HSA was ineffective in this respect. DCLHb infusion restored arterial pressure and increased cardiac index (CI) to 80% of baseline values. Administration of HSA left animals hypotensive (69 mmHg) and increased CI to 122% of the average baseline value. Shock-induced disturbances of the distribution of RMP were improved by administration of DCLHb but not by HSA.

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.

Effect of sevoflurane and desflurane on the myogenic constriction and flow-induced dilation in rat coronary arterioles.

Determinants of myocardial blood flow distribution include metabolic, myogenic, endothelial, and neurohumoral control mechanisms. The authors studied the effect of sevoflurane and desflurane on the myogenic and endothelial mechanisms. Wistar rat subepicardial microvessels, approximately 100 microm in diameter, were monitored for diameter changes in vitro using a video detection system. Myogenic vasomotion was studied by varying the intraluminal pressure from 10 mmHg to 120 mmHg. Flow-induced, endothelium-dependent dilation was evaluated in U46619-preconstricted vessels by varying the pressure gradient across the isolated vessel from 10 mmHg to 80 mmHg, while maintaining the midpoint luminal pressure constant at 40 mmHg to avoid myogenic effects. Myogenic and flow-induced vasomotion both were studied in the presence of sevoflurane, 1 or 2 minimum alveolar concentration (MAC) (MAC is a unit of inhalational anesthetic potency), desflurane, 1 or 2 MAC, or no anesthetic (control). Myogenic constriction was shown above intraluminal pressures of 70 mmHg. Myogenic constriction was unchanged by sevoflurane, 1 MAC (P = 0.24), but was mildly enhanced by sevoflurane, 2 MAC (P < 0.05), or desflurane, 1 (P < 0.05) or 2 MAC (P < 0.01). Flow-induced dilation was shown over the pressure gradient range of 10-80 mmHg. Flow-induced dilation was not altered significantly by sevoflurane, 1 or 2 MAC (P > 0.3 each), but was significantly attenuated by desflurane, 1 or 2 MAC (P < 0.001 each). Sevoflurane maintains myogenic and endothelial determinants of myocardial blood flow distribution. Conversely, desflurane attenuates endothelium-dependent flow-induced dilation while mildly enhancing myogenic constriction.

HIGH THORACIC EPIDURAL ANALGESIA (HTEA)

Introduction: We have demonstrated that HTEA is effective both acutely and chronically in relieving the symptoms of medically and surgically refractory angina pectoris. [1] However, the mechanism by which HTEA reduces angina pectoris during long term treatment has not been established. Therefore, we used stress thallium testing to evaluate improvement in myocardial blood flow during stress induced ischemia. Methods: In a retrospective fashion, 6 patients who had chronic (> 2 months) indwelling implantable epidural catheters were evaluated via pre-insertion and post- implant stress thallium perfusion studies. Results: Two of six patients had improvement, but not resolution of stress induced ischemia at 8 and 12 months, respectively. The remaining four patients had no change in stress induced ischemia. None of the six patients had any new areas of ischemia or infarction as determined by their stress thalliums. (Table 1)Table 1Conclusions: HTEA does relieve the pain of angina pectoris in patients who are refractory to medical and surgical management. [1] The data does not support a significant improvement in myocardial blood flow distribution during stress. However, there is no evidence that disease progression occurs since no patients had evidence of new areas of ischemia or infarctions.

An adenosine agonist and preconditioning shift the distribution of myocardial blood flow in conscious pigs.

The goal of this study was to determine whether the cardioprotective effects of an A1-receptor agonist and ischemic preconditioning (IPC) involve a shift in the pre-coronary artery occlusion (CAO) spatial distribution of myocardial blood flow, which might shed light on the mechanism of IPC and explain its heterogeneous effects. Accordingly, 60 min of CAO followed by 72 h of coronary artery reperfusion (CAR) was examined in three groups of conscious pigs 10-14 days after instrumentation with aortic and left atrial catheters and coronary artery occluders. Myocardial infarct size, expressed as a fraction of the area at risk (AAR), was reduced significantly (P < 0.05) by infusion of the A1 agonist (27.1 +/- 6.6%) and to a greater extent (P < 0.05) by IPC (11.6 +/- 5.1%) compared with infarct size in vehicle-treated animals (55.1 +/- 2.9%). Transmural myocardial blood flow (radioactive microspheres) in the AAR shifted toward lower levels after infusion of the A1 agonist (1.27 +/- 0.19 vs. 0.74 +/- 0.10 ml. min-1. g-1) or IPC (1.27 +/- 0.11 vs. 0.96 +/- 0.09 ml. min-1. g-1) but not after infusion of the vehicle (1.20 +/- 0.10 vs. 1.23 +/- 0.09 ml. min-1. g-1). This study demonstrated that both pretreatment with an adenosine A1 agonist and also IPC altered the spatial distribution of pre-CAO myocardial blood flow, which might reflect a downregulation of metabolic state and thus play a role in the cardioprotective effects of IPC.

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery.

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.