Segment Shortening Research Articles

Smaller infarct after preconditioning does not predict extent of early functional improvement of reperfused heart.

We evaluated the ability of ischemic preconditioning to restore function to salvaged myocardium in rabbits. Although ischemic preconditioning reduces infarct size, few investigators studying recovery of function after coronary occlusions lasting >/=30 min have reported any mechanical benefit in preconditioned hearts. However, because myocardial function was seldom evaluated beyond 5 h after reperfusion stunning may have masked the benefit. Accordingly, rabbits were chronically instrumented with a pneumatic occluder around a branch of the left coronary artery, a pair of 1-mm ultrasonic crystals in the myocardial territory destined to become ischemic, and electrocardiogram (ECG) leads. One week after surgery the ECG and segment length tracing were recorded at rest, during 30-min occlusion and 1 h of reflow, and again at 24, 48, and 72 h. In ischemically preconditioned rabbits, 5-min coronary occlusion and 10-min reperfusion preceded the long occlusion. The beginning and end of systole were determined by recording the first and second heart sounds with a hand-held precordial microphone. Postmortem infarct size was measured with triphenyltetrazolium chloride. During the 30-min coronary occlusion all segments became nearly akinetic or bulged during systole. After 60 min of reflow there was little return of function in either group. Between 24 and 72 h there was minimal recovery in the control group (segment shortening equals 13.3 +/- 4.1% of baseline), whereas function was much better in preconditioned hearts (44.2 +/- 7.4% of baseline, P < 0.02). Infarct size as a percentage of risk zone was much smaller in preconditioned hearts (10.2 +/- 1.4 vs. 29.7 +/- 1.8%, P < 0.001). Thus there is a gradual recovery of systolic function of reperfused myocardium after a coronary occlusion. Although early mechanical recovery is significantly better after preconditioning, it is much less than would be predicted by the reduction of infarct size.

Participation of angiotensin II and bradykinin in contractile function in dog stunned myocardium

We examined the effects of enalapril and 4′-[(1,4′-dimethyl-2′-propyl-[2,6′-bi-1H-enzimidazole]-1′-yl)methyl]-[1,1′-biphenyl]-2-carboxylic acid (BIBR-277), an angiotensin II receptor antagonist, on contractile dysfunction in the stunned myocardium. Dogs were subjected to 20-min ligation of the coronary artery, followed by 60-min reperfusion. Saline, enalapril (1 mg/kg or 3 mg/kg), or BIBR-277 (3 mg/kg) was injected i.v. 10 min before ligation. d-Arginyl- l-arginlyl- l-prolyl- trans-4-hydroxy- l-prolylglycyl-3-(2-thienyl)- l-alanyl- l-seryl- d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl- l-(2α, 3β, 7aβ)-octahydro-1H-indole-2-carbonyl- l-arginine (Hoe-140), a bradykinin B 2 receptor antagonist, at 300 μg/kg was injected i.v. 10 min before drug injection. Contractile function was assessed on the basis of percentage segment shortening (%SS). ATP levels were measured in 60-min reperfused hearts. %SS significantly decreased during ischemia, and recovered during reperfusion, although the %SS was significantly less than the pre-ischemic level. Both enalapril at either dose and BIBR-277 significantly enhanced %SS recovery during reperfusion, an effect which was associated with a tendency toward energy preservation. Hoe-140 completely abolished the effect of enalapril at either dose, while it did not modify that of BIBR-277. Inhibition of angiotensin II formation and bradykinin breakdown may be separately related to the improvement of myocardial stunning.

Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C?

Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs. Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals. There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs. The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Background. We tested the hypothesis that pacing-induced cardiac failure of hypertrophic hearts would reduce the functional and metabolic responses of these hearts to guanylate cyclase inhibition and this was associated with alterations in cyclic GMP.Materials and methods. Methylene blue (MB, 2 mg/kg/min, guanylate cyclase inhibitor) was infused into the left anterior descending coronary artery in 5 control, 5 left ventricular hypertrophy (LVH), and 5 LVH pacing-induced failure dogs. Regional myocardial work was calculated as the integrated product of force and segment shortening and regional myocardial O2 consumption (VO2) from coronary blood flow and O2 extraction measurements. Cyclic GMP was determined by radioimmunoassay.Results. MB increased regional work (635 ± 169 vs 1649 ± 500, 781 ± 184 vs 1569 ± 203 g ∗ mm/min) and VO2 (8.3 ± 1.4 vs 10.9 ± 1.4, 7.3 ± 0.7 vs 9.1 ± 0.7 ml O2/min/100 g) in both control and LVH dogs but not in failure dogs (536 ± 234 vs 623 ± 193, 3.6 ± 1.1 vs 4.7 ± 1.9). MB also decreased cyclic GMP in control dogs (1170 ± 142 vs 812 ± 105 pmol/g). LVH dogs had elevated baseline cyclic GMP (5875 ± 949) compared to control dogs but also demonstrated decreased cyclic GMP in response to MB (2820 ± 372). In failure dogs, basal cyclic GMP was also elevated (4650 ± 613) compared to control dogs but there was a lack of response to MB (3670 ± 640).Conclusions. We conclude that the myocardial function, VO2 and cyclic GMP responses to methylene blue are diminished in the transition from hypertrophy to cardiac failure.

The role of ATP-sensitive potassium channels in the mechanism of ischemic preconditioning.

We clarified the role of K(ATP) channels in the mechanism of ischemic preconditioning by using K(ATP) channel opener, nicorandil, and K(ATP) channel inhibitor, glibenclamide. Forty anesthetized dogs were divided into five groups: (a) control (C), (b) ischemic preconditioning (PC), (c) intravenous infusion of nicorandil before PC (Ni), (d) glibenclamide pretreated with PC (Gl + PC), and (e) glibenclamide pretreated with Ni (Gl + Ni). All groups were followed by 60-min ischemia and 60-min reperfusion and analyzed by the biochemical procedures. At the end of 60-min reperfusion, percentage of segment shortening in C indicated paradoxic bulging. This value was significantly recovered in PC and Ni, but it was still negative in Gl + PC and Gl + Ni. Ca2+ -adenosine triphosphatase (ATPase) activity of sarcoplasmic reticulum (SR) was significantly decreased in C. In PC and Ni, this activity was significantly maintained; however, in Gl + PC and Gl + Ni, it was similar to that in C. State III respiration of mitochondria showed similarity to the changes in SR. These results indicated that the K(ATP) channel opener enhanced the effects of ischemic preconditioning, and its blockade abolished these phenomena. We conclude that the ATP-sensitive potassium channel may play one of key roles in the mechanisms of ischemic preconditioning in the dog model.

Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases.

Nitric oxide (NO) has complex effects on myocardial function particularly following ischaemia-reperfusion. The goal of this study was to examine the result of repetitive myocardial stunning on myocardial NO release and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. Propofol anaesthetised pigs underwent ten, 2-min episodes of circumflex artery occlusion (n = 6) or acted as sham operated controls (n = 4). Measurements of segment shortening demonstrated a fall in function in the ischaemic territory to 52.5 +/- 7.3% (mean +/- S.E.M.) of baseline shortening 30 min after the stunning stimulus, recovering to 92 +/- 8.7% 5.5 h later. Function remained stable in sham controls. The change in venous-arterial [NO] between baseline and 6 h reperfusion was found to be significantly different between the two groups (0.2 +/- 0.7 in stunned vs. -4.3 +/- 1.6 microM in shams; P < 0.02). Western blotting and band optical density used to compare tissue from stunned territory (S), non-stunned territory (IC) and sham control animals (SC) demonstrated this was associated with an increase in the expression of both iNOS (S: 93 +/- 13.4, IC: 37 +/- 2.4 and SC: 25 +/- 4 [arbitrary units], P < 0.01 and P = 0.031) and eNOS (S: 104 +/- 7.4, IC; 62.5 +/- 7.4 and SC; 75.7 +/- 0.6, P < 0.03 and P < 0.01) in stunned myocardium. Immunocytochemistry localised iNOS reactivity to vascular smooth muscle cells and cardiomyocytes in stunned tissue and eNOS reactivity to endothelial cells. Recovery from repetitive myocardial stunning is associated with the increased expression of both iNOS and eNOS and would be compatible with a protective role for both these enzymes. This finding has possible relevance for both the late window of ischaemic preconditioning and myocardial hibernation.

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs.

The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol.

Nitric oxide does not modulate the increases in blood flow, O2 consumption, or contractility during CaCl2 administration in canine hearts.

Endothelium-derived nitric oxide (EDNO) has been shown to have vascular, metabolic, and contractile effects in the heart. We evaluated these effects during intracoronary (i.c.) administration of CaCl2 in dogs. The left anterior descending coronary artery of nine anesthetized, open-chest dogs was perfused at controlled pressure (80 mm Hg) with arterial blood. Coronary blood flow (CBF) was measured with a Doppler transducer and segmental shortening (SS) with ultrasonic crystals. Myocardial oxygen consumption (MVO2) and oxygen extraction (EO2) were calculated. Responses were assessed during i.c. infusions of CaCl2 (5, 10, 15 mg min-1) before and after administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 300 micrograms min-1 for 15 min, i.c.). Before L-NAME, CaCl2 caused dose-dependent, proportional increases in SS and MVO2. Although CBF also increased, these responses were less than proportional to those in MVO2, and thus EO2 increased. L-NAME did not alter the cardiac effects of CaCl2. (1) CaCl2 had direct inotropic and coronary vasoconstricting effects. (2) The vasoconstricting effect impaired coupling of CBF to the augmented metabolic demands by local vasodilating mechanisms. (3) EDNO did not modulate the increases in CBF, MVO2, or SS during administration of CaCl2.

Ischemic preconditioning does not acutely improve load-insensitive parameters of contractility in in vivo stunned porcine myocardium

Objective: Ischemic preconditioning has been shown to have no beneficial effect on segment shortening in in vivo regionally stunned myocardium. The purpose of this study was to determine whether ischemic preconditioning improves the recovery of postischemic ventricular function when contractility is assessed by load-insensitive measurements including end-systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area in in vivo regionally stunned porcine myocardium. Methods: Open chest, pentobarbital-anesthetized pigs were used. Regional ventricular function was monitored by measurements of segment shortening, stroke work, end systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area. The control group was submitted to 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion. The preconditioned group underwent 2 cycles of 5-minute left anterior descending coronary artery occlusion and 10-minute reperfusion before 15 minutes of occlusion. Results: There was no infarct in either group. The preconditioning protocol significantly depressed preischemic segment shortening but not regional stroke work. Ischemic preconditioning had no significant beneficial effect on regional stroke work, end-systolic pressure length relations, preload recruitable stroke work, or preload recruitable stroke work area. Conclusions: These results confirm that ischemic preconditioning does not ameliorate in vivo porcine myocardial stunning and indicate that ischemic preconditioning may have a limited cardioprotective role during cardiac operation. (J Thorac Cardiovasc Surg 1999;117:810-7)

Changes in passive but not active mechanical properties predict recovery of function of stunned myocardium.

The time course of alterations in active and passive mechanical properties of stunned myocardium during ischemia and throughout reperfusion has not been thoroughly quantified. This investigation tested the hypothesis that the amount of injury as well as the rate and extent of recovery of contractile function in postischemic, reperfused myocardium are directly correlated to changes in regional active and passive elastance and viscosity. A modified viscoelastic Voigt model was employed to quantify myocardial mechanical properties. Left ventricular pressure and segment length (in both ischemic and normal regions) were fit to the model consisting of an active elastic spring in parallel with a viscous damper and a passive elastic spring. The mechanical properties of myocardium from dogs which recovered (> or = 50%) baseline regional contractile function as determined by percent segment shortening (n=7) were compared to those from dogs that did not recover function (n=7). Both groups displayed decreased active elastance in the ischemic region during coronary artery occlusion, and this decrease was maintained in the nonrecovery group. Increases in viscosity of ischemic myocardium were observed in both groups during coronary occlusion but returned to control only in the recovery group. The nonrecovery group demonstrated increased passive elastance in the ischemic region during coronary occlusion and throughout the reperfusion period whereas the recovery group remained unchanged. We conclude that functional recovery of stunned myocardium is directly related to alterations in mechanical properties caused by ischemia and that changes in passive elastance during occlusion may predict the ability of ischemic myocardium to recover contractile function.

Early contrast-enhanced MRI predicts late functional recovery after reperfused myocardial infarction.

We have observed 3 abnormal patterns on contrast-enhanced MRI early after reperfused myocardial infarction (MI): (1) absence of normal first-pass signal enhancement (HYPO), (2) normal first pass signal followed by hyperenhanced signal on delayed images (HYPER), or (3) both absence of normal first-pass enhancement and delayed hyperenhancement (COMB). This study examines the association between these patterns in the first week after MI and late recovery of myocardial contractile function by use of magnetic resonance myocardial tissue tagging. Seventeen patients (14 men) with a mean age of 53+/-12 years were studied after a reperfused first MI. Contrast-enhanced images were acquired immediately after bolus administration of gadolinium and 7+/-2 minutes later. Tagged images were acquired at weeks 1 and 7. Circumferential segment shortening (%S) was measured in regions displaying HYPER, COMB, or HYPO contrast patterns and in remote regions (REMOTE) at weeks 1 and 7. At week 1, %S was depressed in HYPER, COMB, and HYPO (9+/-8%, 7+/-6%, and 5+/-4%, respectively) and were less than REMOTE (18+/-6%, P<0.003). However, in HYPER, %S improved at week 7 from 9+/-8% to 18+/-5% (P<0.001 versus week 1). In contrast, HYPO did not improve significantly (5+/-4% to 6+/-3%, P=NS) and COMB tended to improve 7+/-6% to 11+/-6% (P=0.06). HYPER has partially reversible dysfunction and represents predominantly viable myocardium. COMB shows borderline improvement and likely contains an admixture of viable and necrotic myocardium. HYPO shows little functional improvement at 7 weeks, presumably because of irreversible myocardial damage.

Intracoronary propofol attenuates myocardial but not coronary endothelial dysfunction after brief ischaemia and reperfusion in dogs

We have investigated the effects of propofol on recovery of regional mechanical and coronary endothelial function and on lipid peroxidation in post-ischaemic myocardium in dogs. The animals were assessed for 180 min during reperfusion after 15-min of occlusion of the left anterior descending coronary artery (LAD). They were treated with intracoronary (i.c.) propofol 5 or 20 micrograms/ml of coronary flow or vehicle (control group) for 60 min, beginning 30 min before LAD occlusion. Propofol significantly enhanced recovery of regional contractile function (70% and 81% of baseline segment shortening in the propofol 5 and 20 micrograms ml-1 groups, respectively, compared with 51% in controls at 3 h of reperfusion). However, LAD flow responses to i.c. acetylcholine were similarly attenuated regardless of treatment with propofol throughout reperfusion. The increase in malondialdehyde induced by ischaemia-reperfusion was significantly suppressed by both doses of propofol. These results demonstrated that in vivo, propofol ameliorated dysfunction of the myocardium but not of the coronary endothelium resulting from brief ischaemia and reperfusion; the protection may be related, at least in part, to its ability to reduce lipid peroxidation.

The angiotensin II AT1 receptor antagonist candesartan at antihypertensive plasma concentrations reduces damage induced by ischemia-reperfusion.

The aim of this study was to investigate if the angiotensin II AT1 receptor antagonist candesartan in antihypertensive plasma concentrations improves myocardial function and limits infarct size in anesthetized pigs. Animals were subjected to 45 min of regional ischemia and 240 min of reperfusion. Starting 60 min before ischemia, two groups of pigs (n = 6 in each) received either candesartan (25 micrograms/kg bolus followed by a continuous infusion at a rate of 14 micrograms/kg/h) or the corresponding volume of vehicle throughout the study period. Left ventricular systolic segment shortening (%SS) was measured by sonomicrometry, and infarct size was determined by triphenyl tetrazolium chloride staining. The plasma concentration of candesartan during the experiment was between 100 and 150 nmol/L, which was considered to be within the therapeutic range. Neither candesartan nor vehicle affected hemodynamics or coronary blood flow prior to ischemia. Compared to vehicle, candesartan improved recovery of %SS in the ischemic area. At 240 min of reperfusion, the %SS was significantly higher in pigs given candesartan than in pigs given vehicle (7.1 +/- 0.87% vs-1 +/- 1.79%; p < 0.01). In both groups the area at risk was approximately 20% of the left ventricle. Infarct size as a percentage of the area at risk was significantly smaller in the candesartan group than in the vehicle group (46 +/- 3.0 vs 73 +/- 3.6%; p < 0.01). The results suggest that angiotensin II AT1 receptor blockade, obtained in antihypertensive plasma concentrations, supports myocardial functional recovery and limits infarct size.

Effect of sialyl Lewis x oligosaccharide on myocardial and cerebral injury in the pig

Background. Although administration of the sialyl Lewis x oligosaccharide may reduce myocardial injury after ischemia–reperfusion, its effect on coronary and cerebral microvascular regulation and its clinical application during cardiac operation have not been examined. Methods. Pigs were placed on normothermic cardiopulmonary bypass after 30 minutes of left anterior descending coronary artery occlusion. The hearts were then arrested with cold high potassium cardioplegia. After 1 hour the cross-clamp was removed and the pigs were weaned from cardiopulmonary bypass and perfused for an additional 1 hour. CY-1503 (a sodium salt of the sialyl Lewis X oligosaccharide, n = 6) was administered before reperfusion. Six other pigs received saline vehicle. Endothelium-dependent relaxation of precontracted coronary and brain arterioles (70 to 180 μm) to adenosine 5′-diphosphate and endothelium-independent relaxation to sodium nitroprusside were studied in vitro with videomicroscopy. Control values were obtained from uninstrumented pigs. Myeloperoxidase activity in the myocardium and brain was measured to quantify neutrophil infiltration. Cardiac function and perfusion were assessed by left ventricular systolic pressure, maximum rate of increase of left ventricular pressure, left anterior descending coronary artery blood flow and percent segmental shortening, and cerebral vascular resistance, internal carotid artery blood flow, and the constitutively expressed and inducible isoform of nitric oxide synthase mRNA were measured. Results. The impaired myocardial contractile function after ischemia and cardioplegia was not improved by administration of CY-1503. The reduced endothelium-dependent relaxation responses of coronary and brain arterioles during ischemia followed by cardioplegia and cardiopulmonary bypass were improved with CY-1503, but the altered pattern of organ perfusion was not improved. Myeloperoxidase activity was increased in the heart after ischemia–cardioplegia and in the brain after cardiopulmonary bypass. CY-1503 reduced myeloperoxidase activity in both the myocardium and in the brain. Expressions of myocardial inducible isoform or constitutively expressed nitric oxide synthase were not altered in the heart. Conclusions. Although the sialyl Lewis x oligosaccharide does reduce neutrophil infiltration and endothelial injury in the coronary and cerebral microcirculation after cardiopulmonary bypass, it does not have significant beneficial acute effects on organ perfusion or function in the myocardium or brain.

The relationship between regional blood flow and contractile function in normal, ischemic, and reperfused myocardium.

During normoperfusion, both myocardial blood flow and contractile function are heterogeneously distributed throughout the left ventricle, in that midwall segment shortening is higher at the apex than at the base of the left ventricle, and greater in the anterior than in the posterior wall. Also, transmural heterogeneity of myocardial deformation exists with greater segment shortening and wall thickening occurring in inner than in outer myocardial layers. A transmural heterogeneity of myocardial blood flow-with greater inner as compared to outer wall perfusion-exists which is not simply related to temporal fluctuations since the heterogeneous flow pattern is stable over at least a few minutes. While an increase in myocardial contractile function will lead to a metabolically mediated increase in myocardial blood flow, an increase in regional coronary perfusion within or above the autoregulatory range does not increase regional myocardial contractile function. During hypoperfusion, the reduction in subendocardial blood flow is more pronounced than that in subepicardial blood flow, and contractile function in the inner myocardial layers ceases more rapidly than in the outer myocardial layers. The reduced regional myocardial contractile function is closely matched to the reduced regional myocardial blood flow; however, such a coupling between reduced flow and function is lost when ischemia is prolonged for several hours in that function for a given flow is further reduced. During reperfusion, regional myocardial contractile function remains depressed for a prolonged period of time, depending on the severity, duration, and location of the preceding ischemic episode, while regional myocardial blood flow is restored to almost normal. Recovery of contractile function in the outer myocardial layers is faster than in the inner myocardial layers.

Left ventricular dysfunction following rewarming from experimental hypothermia.

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25 degreesC and returned to 37 degreesC over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/dtmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (tau) and the LV wall stiffness constant (Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25 degreesC: dP/dtmax 2,180 +/- 158 vs. 760 +/- 78 mmHg/s, SS% 20.1 +/- 1.2 vs. 13.3 +/- 1.0%, SV 11.7 +/- 0.7 vs. 8.5 +/- 0.7 ml, PRSW 90.5 +/- 7.7 vs. 29.1 +/- 5.9 J/m. 10(-2), Kp 0.78 +/- 0.10 vs. 0.28 +/- 0.03 mm-1, and tau 78.5 +/- 3.7 vs. 25.8 +/- 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25 degreesC persisted: dP/dtmax 1,241 +/- 108 mmHg/s, SS% 10.2 +/- 0.8 J, SV 7.3 +/- 0.4 ml, and PRSW 52.1 +/- 3.6 m. 10(-2), whereas the diastolic values of Kp and tau returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+ trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.

Anti-C5a monoclonal antibody reduces cardiopulmonary bypass and cardioplegia-induced coronary endothelial dysfunction

Objective: Because C5a induces tissue injury by activating polymorphonuclear leukocytes, the hypothesis was that inhibition of C5a activity would reduce cardioplegia-related injury. Methods: Pigs were placed on cardiopulmonary bypass. The hearts were arrested for 1 hour with hyperkalemic cardioplegia. Pigs were then separated from bypass, and the hearts were reperfused for 2 hours. Anti-porcine C5a monoclonal antibody (1.6 mg/kg, intravenously; n = 6) was administered 20 minutes before the onset of cardiopulmonary bypass. Six pigs received saline solution vehicle. Reactivity of coronary arterioles was studied in vitro with videomicroscopy. Microvessels from uninstrumented pigs served as controls for vascular studies. Results: Endothelium-dependent relaxation to adenosine diphosphate (percent relaxation of precontraction) was reduced after cardioplegic reperfusion (63% ± 14% vs 77% ± 10% in control at 10 μmol/L; P = .01). This impairment in endothelium-dependent relaxation was improved with anti-porcine C5a monoclonal antibody (80% ± 22%; P = .01 vs saline solution), as was the impaired endothelium-dependent relaxation to clonidine (64% ± 12% control; 26% ± 17% saline solution; 55% ± 24% anti-porcine C5a monoclonal antibody at 10 μmol/L; P = .01 saline solution vs control or anti-porcine C5a monoclonal antibody). Myeloperoxidase activity was significantly decreased (0.2 ± 0.2 units/g protein; P = .04) in the anti-porcine C5a monoclonal antibody group compared with 5.2 ± 2.7 in the saline solution group. CH 50 2 hours after bypass was not statistically different (0.57 ± 0.41 unit and 0.65 ± 0.41 unit, respectively) between the anti-porcine C5a monoclonal antibody and saline solution groups. Despite less myocardial polymorphonuclear leukocyte infiltration after C5a inhibition, maximum rate of rise of left ventricular pressure, percent segmental shortening, and blood flow through the left anterior descending coronary artery were similar in the anti-porcine C5a monoclonal antibody and saline solution groups. Conclusions: Inhibition of C5a limits neutrophil-mediated impairment of endothelium-dependent relaxation after cardiopulmonary bypass and cardioplegic reperfusion, but it has no effect on short-term myocardial functional preservation. (J Thorac Cardiovasc Surg 1998;116:1060-8)

Influence of Nitric Oxide on Vascular, Metabolic, and Contractile Responses to Dobutamine in In Situ Canine Hearts

The left anterior descending coronary arteries of 30 anesthetized, open-chest dogs were perfused via an extracorporeal circuit. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and segmental shortening (SS) were measured. Studies were performed with coronary perfusion pressure (CPP) or CBF constant. With CPP constant, effects of intracoronary (IC) infusions of dobutamine (2.5, 5.0, or 10.0 [micro sign]g/min) were evaluated alone (control) and after inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester (L-NAME). With CBF constant, a NO donor (sodium nitroprusside [SNP] 80 [micro sign]g/min IC) or nitroglycerin [NTG] 40 [micro sign]g/min IC) or a releaser of endogenous NO (acetylcholine [ACh]; 20 [micro sign]g/min IC) was infused along with dobutamine. Increases in CBF during dobutamine and isoproterenol were compared before and after blockade of beta1-adrenergic receptors with atenolol. Dobutamine caused proportional, dose-dependent increases in CBF, MVO2, and SS, which were not altered by L-NAME. Administration of the NO donors or ACh during dobutamine markedly decreased CPP, but only ACh also reduced SS and MVO2. These latter effects persisted after L-NAME. Atenolol blunted increases in CBF by dobutamine more than those by isoproterenol. We conclude that endogenous NO did not modulate the coronary vasodilation or the increases in myocardial contractility and MVO2 during dobutamine. In addition, neither SNP nor NTG altered myocardial contractility or MVO2 in dobutamine-stimulated myocardium, whereas ACh had a negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. Implications: Endogenous nitric oxide (NO) did not modulate increases in coronary blood flow, myocardial contractility, or myocardial oxygen consumption during intracoronary infusions of dobutamine. The NO donors sodium nitroprusside and nitroglycerin had no effect on contractility or oxygen consumption in dobutamine-stimulated myocardium. Acetylcholine had negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. (Anesth Analg 1998;87:994-1001)

Influence of nitric oxide on vascular, metabolic, and contractile responses to dobutamine in in situ canine hearts.

The left anterior descending coronary arteries of 30 anesthetized, open-chest dogs were perfused via an extracorporeal circuit. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and segmental shortening (SS) were measured. Studies were performed with coronary perfusion pressure (CPP) or CBF constant. With CPP constant, effects of intracoronary (IC) infusions of dobutamine (2.5, 5.0, or 10.0 microg/min) were evaluated alone (control) and after inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester (L-NAME). With CBF constant, a NO donor (sodium nitroprusside [SNP] 80 microg/min IC) or nitroglycerin [NTG] 40 microg/min IC) or a releaser of endogenous NO (acetylcholine [ACh]; 20 microg/ min IC) was infused along with dobutamine. Increases in CBF during dobutamine and isoproterenol were compared before and after blockade of beta1-adrenergic receptors with atenolol. Dobutamine caused proportional, dose-dependent increases in CBF, MVO2, and SS, which were not altered by L-NAME. Administration of the NO donors or ACh during dobutamine markedly decreased CPP, but only ACh also reduced SS and MVO2. These latter effects persisted after L-NAME. Atenolol blunted increases in CBF by dobutamine more than those by isoproterenol. We conclude that endogenous NO did not modulate the coronary vasodilation or the increases in myocardial contractility and MVO2 during dobutamine. In addition, neither SNP nor NTG altered myocardial contractility or MVO2 in dobutamine-stimulated myocardium, whereas ACh had a negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. Endogenous nitric oxide (NO) did not modulate increases in coronary blood flow, myocardial contractility, or myocardial oxygen consumption during intracoronary infusions of dobutamine. The NO donors sodium nitroprusside and nitroglycerin had no effect on contractility or oxygen consumption in dobutamine-stimulated myocardium. Acetylcholine had negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO.

Noninvasive delineation of normal right ventricular contractile motion with magnetic resonance imaging myocardial tagging.

As the importance of the right ventricle in many diseases and conditions has been realized, the need for quantitative assessment of the motion and contraction of the right ventricular free wall (RVFW) has become apparent. This study applied the myocardial tagging magnetic resonance imaging (MRI) technique to the normal RVFW to elucidate normal heterogeneity in RV motion and contractile patterns. The RVFW was divided into three segments (inferior, mid and superior) in each of three slices (apical, mid and basal) to allow for a detailed analysis of the motion and contraction. Percent segmental shortening (PSS) was used to measure the amount of contraction, and a vector analysis was used to quantitate the trajectory of the RVFW through systole. PSS increased monotonically through time to an average across all segments of 12% in the basal slice, 14% in the mid-ventricular slice, and 16% in the apical slice of the heart. The trajectory of the RVFW was characterized by a wave of motion toward the septum and outflow tract. The data provided in this study provide a better understanding of normal RV kinematics and can serve as a comparison for disease states.