Lower Coronary Perfusion Pressure Research Articles

The Effects of Different Doses of Sildenafil on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts.

The dose-response relationship of sildenafil effects on cardiac function is not completely elucidated. The aim of this study was to assess the effects of different doses of sildenafil on coronary flow and oxidative stress in isolated rat hearts. Coronary flow and markers of oxidative stress, including nitrite outflow, and superoxide anion production in coronary effluent, were determined for isolated rat hearts. The experiments were performed during control conditions and in the presence of sildenafil (10, 20, 50, 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). Sildenafil was shown to result in a significant increase in coronary flow at lower coronary perfusion pressure (CPP) values at all administered doses, whereas, with an increase in CPP, a reduction in coronary flow was observed. An increase in nitric oxide (NO) was most pronounced in the group treated with the lowest dose of sildenafil at the highest CPP value. After the inhibition of the NO-cyclic guanosine monophosphate (cGMP) signaling (NOS) system by L-NAME, only a dose of 200 nM sildenafil was high enough to overcome the inhibition and to boost release of O2-. That effect was CPP-dependent, with statistical significance reached at 80, 100 and 120 mmHg. Our findings indicate that sildenafil causes changes in heart vasculature in a dose-dependent manner, with a shift from a vasodilatation effect to vasoconstriction with a pressure increase. The highest dose administered is capable of producing superoxide anion radicals in terms of NOS system inhibition.

Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. The 158 patients (56.7 ± 13.6years, 28.5% female) studied had a median CPP of 40mmHg (IQR 35-52mmHg). During 6months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

CORONARY PERFUSION PRESSURE GRADIENT IS ASSOCIATED WITH INCREASED ADVERSE OUTCOMES IN PATIENTS WITH ADVANCED HEART FAILURE

Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) is associated with adverse outcomes in heart failure Outcomes in patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary

Impact of pre–stage II hemodynamics and pulmonary artery anatomy on 12-month outcomes in the Pediatric Heart Network Single Ventricle Reconstruction trial

To compare the interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for the Pediatric Heart Network Single Ventricle Reconstruction trial. The trial, which randomized subjects to a modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated the RVPAS was associated with a smaller pulmonary artery diameter but superior 12-month transplant-free survival. We analyzed the pre-stage II catheterization data for the trial subjects. The hemodynamic variables and shunt and pulmonary angiographic data were compared between shunt types; their association with 12-month transplant-free survival was also evaluated. Of 549 randomized subjects, 389 underwent pre-stage II catheterization. A smaller size, lower aortic and superior vena cava saturation, and higher ventricular end-diastolic pressure were associated with worse 12-month transplant-free survival. The MBTS group had a lower coronary perfusion pressure (27 vs 32 mm Hg; P<.001) and greater pulmonary blood flow/systemic blood flow ratio (1.1 vs 1.0, P=.009). A greater pulmonary blood flow/systemic blood flow ratio increased the risk of death or transplantation only in the RVPAS group (P=.01). The MBTS group had fewer shunt (14% vs 28%, P=.004) and severe left pulmonary artery (0.7% vs 9.2%, P=.003) stenoses, larger mid-main branch pulmonary artery diameters, and greater Nakata indexes (164 vs 134, P<.001). Compared with the RVPAS subjects, the MBTS subjects had more hemodynamic abnormalities related to shunt physiology, and the RVPAS subjects had more shunt or pulmonary obstruction of a severe degree and inferior pulmonary artery growth at pre-stage II catheterization. A lower body surface area, greater ventricular end-diastolic pressure, and lower superior vena cava saturation were associated with worse 12-month transplant-free survival.

Old and New Intravenous Inotropic Agents in the Treatment of Advanced Heart Failure

Inotropic agents are administered to improve cardiac output and peripheral perfusion in patients with systolic dysfunction and low cardiac output. However, there is evidence of increased mortality and adverse effects associated with current inotropic agents. These adverse outcomes may be ascribed to patient selection, increased myocardial energy expenditure and oxygen consumption, or to specific mechanisms of action. Both sympathomimetic amines and type III phosphodiesterase inhibitors act through an increase in intracellular cyclic adenosine monophoshate and free calcium concentrations, mechanisms that increase oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation with some agents (phosphodiesterase inhibitors and levosimendan) may also lower coronary perfusion pressure and favor myocardial damage. New agents with different mechanisms of action might have a better benefit to risk ratio and allow an improvement in tissue and end-organ perfusion with less untoward effects. We have summarized the characteristics of the main inotropic agents for heart failure treatment, the data from randomized controlled trials, and future perspectives for this class of drugs.

Part 13: pediatric basic life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Part 13: pediatric basic life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Abstract P16: The Decreases of Left Ventricle Volume and Area During VF Affect Resuscitation Outcomes

Introduction: Dynamic changes in dimensions of left ventricle (LV) during cardiac arrest might influence the efficacy of CPR. However, the relationships between change in LV dimensions during cardiac arrest and CPR hemodynamic and outcomes remain to be studied. In the present study, we investigated changes of left ventricular volume and area during prolonged untreated ventricular fibrillation (VF) and related those change to coronary perfusion pressure (CPP) during CPR and resuscitation outcomes. Hypothesis: Decreased LV volume and area during prolonged VF interval would yield low CPP and poor resuscitation outcomes. Methods: In 12 domestic male pigs weighing 40±3 kg, VF was electrically induced and untreated for 15 min. CPR was performed for a 5 min interval prior to defibrillation. CPR was continued until return of spontaneous circulation (ROSC) or for a max of 15 minutes. Diastolic aortic and right atrial pressures were measured and CPP was calculated. LV dimensions were continuously assessed by echocardiographic measurement during the 15 minutes of untreated VF. Results: 6 animals were successfully resuscitated. During the 15 minute interval of VF, LV area and volume reduced in all the animals. In animals that were not resuscitated LV dimensions were significantly lower compared to those in resuscitated animals (p=0.01). These differences were observed after 10 minutes of untreated VF. The animals with greater reduction in LV dimension during VF, achieved significantly lower CPP during CPR in contrast to animals with larger LV during VF (Table ). Conclusion: Greater decrease in LV volume and area during cardiac arrest are associated with low CPP during CPR and poor resuscitation outcome. LV dimensions prior to start CPR might therefore affect the effectiveness of resuscitation interventions.

Abstract 30: Incomplete Chest Recoil During Piglet CPR Worsens Hemodynamics

Background : Incomplete chest recoil during cardiopulmonary resuscitation (CPR) (ie, leaning on the chest during the decompression phase) is purported to decrease venous return, and thereby decrease forward blood flow. Aim To determine the effect of 10% and 20% lean on hemodynamics during piglet CPR. Methods : 10 piglets (10.7±1.2 kg) were anesthetized with isoflurane and instrumented with micromanometer-tipped catheters in the right atrium (RA) and aorta (Ao). After induction of ventricular fibrillation, CPR was provided in three-minute epochs with no lean, 10% lean, or 20% lean while aortic systolic pressure (AoS) was targeted at 80–90 mmHg. Because the mean force to attain 80 –90 mm Hg AoS was 18 kg in preliminary studies, 10% and 20% lean were provided as 1.8 and 3.6 kg weights on the chest, respectively. Left ventricular myocardial blood flow (MBF) and cardiac index (CI) were determined by fluorescent, color-microsphere technique. Statistics: paired t -test and repeated measurement ANOVA for parametric, Wilcoxon Rank Sum Test and Friedman’s ANOVA for non-parametric data. Results : 10% and 20% lean resulted in higher right atrial diastolic pressure (RAD) and lower coronary perfusion pressure (CPP) than no lean. Hemodynamics were not different with 10% lean vs. 20% lean. Mean 10%–20% lean resulted in substantially lower MBF and CI than no lean (Table ). Conclusions : 10–20% leaning during CPR increases RAD, decreases CPP, and substantially decreases MBF and CI. Table

Effects of single-ventricle physiology with aortopulmonary shunt on regional myocardial blood flow in a piglet model

In single-ventricle physiology with aortopulmonary connection, diastolic hypotension could alter regional myocardial blood flow. Also, afterload increases could impair myocardial blood flow by increased wall tension and relative subendocardial malperfusion. This study explores the effects of acute single-ventricle physiology on regional myocardial blood flow distribution and investigates the consequences of moderate afterload augmentation on myocardial blood flow. Single-ventricle physiology was created in 8 piglets without using bypass, and 8 animals served as a sham control group. Aortopulmonary shunt, echo-guided atrial septostomy, tricuspid valve avulsion, and pulmonary artery occlusion allowed the left ventricle to support systemic and pulmonary circulations. Afterload augmentation was produced by aortic balloon inflation. Physiologic recordings and stable-isotope microsphere determination of myocardial blood flow to the subepicardium and subendocardium were obtained at baseline and during single-ventricle physiology (at 30 minutes, 120 minutes, and afterload increase). Arterial oxygen content, diastolic pressure, and coronary perfusion pressure declined after creation of single-ventricle physiology (P < .05). Acute single-ventricle physiology resulted in higher myocardial blood flow (P < .05), unchanged subendocardial/subepicardial flow ratio and oxygen delivery, and lower coronary resistance (P < .01) as compared with biventricular physiology. Afterload augmentation increased coronary perfusion pressure, causing a trend for higher myocardial blood flow and oxygen delivery (P = NS), without affecting subendocardial/subepicardial flow distribution. Myocardial oxygen supply/demand balance fell in single-ventricle physiology, remaining unchanged during afterload augmentation. Our study demonstrates that, in acute single-ventricle physiology with aortopulmonary shunt, myocardial blood flow is maintained by lower coronary perfusion pressure. Further, single-ventricle physiology results in less favorable myocardial oxygen supply/demand balance, although normal transmural myocardial blood flow distribution is maintained. Avoidance of diastolic runoff (ventricle-pulmonary conduit) could improve coronary reserve. In our study, moderate afterload augmentation did not induce relative subendocardial malperfusion, nor did it worsen oxygen supply/demand balance.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 +/- 4.1) than in Sh8 (100.8 +/- 1.3), but comparable between aortocaval fistula 4 (50.0 +/- 8.9) and Sh4 (84.8 +/- 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r(2) = .86, P <.001), whereas left ventricular systolic pressure (r(2) = 0.73, P = .004) and end-diastolic pressure (r(2) = 0.55, P = 012) correlated positively and independently with interstitial fibrosis. Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.

Cellular mechanisms of cardioprotection afforded by inhibitors of angiotensin converting enzyme in ischemic hearts: role of bradykinin and nitric oxide.

Angiotensin converting enzyme (ACE) inhibitors inhibit the degradation of bradykinin and contribute to accumulation of bradykinin and NO, both of which may be beneficial for diseased hearts. To test this idea, we administered imidaprilat and cilazaprilat, respectively to the canine ischemic myocardium. In the open chest dogs with low constant coronary perfusion pressure (CPP, from 104 +/- 3 to 42 +/- 3 mmHg), coronary blood flow (CBF, 91 +/- 1 to 32 +/- 2 ml/100 g/min), fractional shortening (FS), and lactate extraction ratio (LER) decreased. Either imidaprilat or cilazaprilat increased CBF, FS, and LER with increases in cardiac bradykinin and NO levels. The beneficial effects of ACE inhibitors were blunted by either L-NAME (an inhibitor of NO synthase) and HOE140 (an inhibitor of bradykinin receptors), respectively. ACE inhibitors, on the other hand, are reported to attenuate the severity of myocardial stunning, which effect is partially attributable to bradykinin- and NO-dependent mechanisms. Further, ACE inhibitors limited infarct size following coronary occlusion and reperfusion. This infarct size-limitation was blunted by either L-NAME and IBTX (the antagonist of K(Ca) channels). Bradykinin is also reported to close K(Ca) channels. Thus, we concluded that ACE inhibitors attenuate both reversible and irreversible myocardial cellular injury via bradykinin/NO-dependent mechanisms. In experimental and clinical settings, the cardioprotective effects of ACE inhibitors on the diseased heart may be attributable to these mechanisms.

Protectant activity of defibrotide in cardioplegia followed by ischemia/reperfusion injury in the isolated rat heart.

Previous studies have shown that defibrotide, a polydeoxyribonucleotide obtained by depolymerization of DNA from porcine tissues, has important protective effects on myocardial ischemia, which may be associated with a prostacyclin-related mechanism. The purpose of this study was to investigate the direct effects of defibrotide (given in cardioplegia or after ischemia) on a model of rat heart recovery after cardioplegia followed by ischemia/reperfusion injury. Isolated rat hearts, undergoing 5 minutes of warm cardioplegic arrest followed by 20 minutes of global ischemia and 30 minutes of reperfusion, were studied using the modified Langendorff model. The cardioplegia consisted of St. Thomas' Hospital solution augmented with defibrotide (50, 100, and 200 microg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha; the stable metabolite of prostacyclin) were measured during preischemic and reperfusion periods. After global ischemia, hearts receiving defibrotide in the cardioplegic solution (n = 8) manifested in a concentration-dependent fashion lower left ventricular end-diastolic pressure (p < 0.001), higher left ventricular developed pressure (p < 0.01), and lower coronary perfusion pressure (p < 0.001) compared to the control group. After reperfusion, hearts receiving defibrotide in the cardioplegic solution also had, in a dose-dependent way, lower levels of creatine-kinase (p < 0.01), lactate dehydrogenase (p < 0.001), and higher levels of 6-keto-PGF1alpha (p < 0.001) compared to the control group. Furthermore, when defibrotide was given alone to the hearts at the beginning of reperfusion (n = 7), the recovery of postischemic left ventricular function was inferior (p < 0.05) to that obtained when defibrotide was given in cardioplegia. Defibrotide confers to conventional crystalloid cardioplegia a potent concentration-dependent protective effect on the recovery of isolated rat heart undergoing ischemia/reperfusion injury. The low cost and the absence of contraindications (cardiac toxicity and hemodynamic effects) make defibrotide a promising augmentation to cardioplegia.

Restenosis after Angioplasty in Patients with Left Ventricular Dysfunction

Clinical and angiographic rates of restenosis after angioplasty were compared in 80 patients (group A) with ejection fractions below 40% (mean, 28.3% ± 5.2%) and 50 (group B) with ejection fractions above 50% (mean, 58% ± 5.4%). Mean angina class improved to the same degree in both groups after angioplasty. Recurrence of significant angina within 6 to 12 months affected 30 patients (38%) in group A compared to 12 (24%) in group B (p &gt; 0.05). Angiographic restenosis occurred in 42 patients (53%) in group A compared to 14 (28%) in group B (p = 0.006). Restenosis after single-vessel angioplasty was 46% in group A and 25% in group B (p &gt; 0.05), after multivessel angioplasty it was 62% in group A and 33% in group B (p = 0.05). In group A, restenosis was more frequent in the left anterior descending coronary artery (46%) compared to the right coronary (41%) or circumflex (30%). Higher rates of restenosis occurred in patients with prior coronary artery bypass grafting (64%) or recanalization of chronic total occlusion (61%). Angina was a less reliable indication of restenosis in group A. We attribute the higher rate of restenosis in patients with low ejection fractions partly to low coronary perfusion pressure.

Aging, Changes in the Cardiovascular System, and Responses to Stress

I have presented a picture of cardiovascular aging that resembles the situation with vision, where in the absence of actual disease, near vision changes with age and cataracts appear with age but after these are corrected, vision remains markedly unchanged with age. For the undiseased heart, intrinsic cardiac muscle function and the inotropic response to nonsympathetic mediators, along with coronary perfusion, are well maintained with age. There are, however, some changes that do occur with age. Cellular hypertrophy occurs, both because of cell drop out and because of some chamber hypertrophy secondary to increased impedance to left ventricular ejection. As a result of the hypertrophy, there is some prolongation of systole secondary to delayed relaxation. This is typical of what occurs in hypertension induced hypertrophy as well. These age-related changes are of critical importance and are the background for the entire discussion of the interplay between hypertension and disease. The large arteries do in fact stiffen with age. Thus, even without hypertension, there is an age-related increased impedance to ejection, a greater systolic load, a lower coronary perfusion pressure, and an increased pulse wave velocity. Added to this is the failure of the entire beta-sympathetic system to respond as well in the elderly as in the younger individuals with a resultant decrease in the vasodilating response. Both the chronotropic and inotropic response to sympathetic mediation is diminished so that states that put sudden loads on the left ventricle, such as accelerated hypertension or myocardial infarction, have more severe results in the elderly. Also acute hypertension may produce less hypertrophy in the elderly and therefore place more hemodynamic stress on the left ventricle than in young adults.

Role of endogenous renin-angiotensin system in c-fos activation and PKC-epsilon translocation in adult rat hearts.

Myocardial stretch and the renin-angiotensin system have been implicated in the development of cardiac hypertrophy through the activation of specific target genes. However, the relative importance of these putative hypertrophic stimuli has not been established in vivo. We used an isolated isovolumic heart preparation in which coronary perfusion pressure (CPP), left ventricular end-diastolic pressure, and pharmacological therapy can be independently manipulated to study this relationship. High CPP (140 cmH2O), which increased coronary flow (8.99 vs. 17.6 ml/min) and left ventricular systolic pressure (50 vs. 91 mmHg), increased steady state c-fos mRNA expression 2.3-fold (all P < 0.01 vs. low CPP). In contrast, increased left ventricular end-diastolic pressure (25 mmHg) and/or infusion of angiotensin II in the absence of increased CPP was not associated with an increase in c-fos mRNA expression. The change in c-fos gene expression seen with increased CPP was largely reversed by treatment with an angiotensin type 1 (AT1) receptor blocker. Hearts perfused at high CPP demonstrated increased translocation/activation of protein kinase C-epsilon relative to controls. None of the hearts studied were ischemic during perfusion. Thus, in the perfused adult rat heart, dynamic, but not static, stretch activates the early response gene, c-fos, and may involve the endogenous reninangiotensin system and protein kinase C.

Effects of hypertrophy and heart failure on [Na +] i in pressure-overloaded guinea pig heart

Intracellular free sodium levels ([Na+]i) were assessed with 23Na nuclear magnetic resonance (NMR) spectroscopy in isolated, Langendorff-perfused normal, compensated hypertrophied, and hypertrophied failing guinea pig hearts under several conditions. Baseline [Na+]i measured with a shift reagent was significantly greater than normal in the compensated hypertrophied hearts (12.8 +/- 1.2 mmol/L v 6.4 +/- 0.7 mmol/L, means +/- SEM, P < .01), but not in the hypertrophied failing hearts (8.7 +/- 1.9 mmol/L, P = N.S.). Moreover, the highest levels of [Na+]i were seen just 3 to 4 weeks after aortic constriction. [Na+]i was inversely related to both time after aortic constriction (R = -0.71, P < .03) and to the degree of left ventricular hypertrophy (R = -0.79, P < .01), suggesting that the hypertrophied failing heart is capable of maintaining relatively normal [Na+]i. In addition, triple quantum filtered NMR measurements were made to assess changes in [Na+]i subsequent to altered perfusion or loading conditions. In hypertrophied failing hearts, but not normal hearts, low coronary perfusion pressure (60 cm H2O) was associated with relatively higher [Na+]i (ANOVA, P < .05), suggesting greater sensitivity of hypertrophied failing hearts to hypoperfusion. On the other hand, when all hearts were perfused at 90 cm H2O and intraventricular balloon volume was increased from 100 microL to 300 microL, [Na+]i increased significantly only in the normal guinea pig hearts (12.3 +/- 1.8%, P < .01). These findings suggest complex changes in the expression or modulation of proteins involved in Na+ regulation. Interpretation regarding the physiological significance of these changes depends on the specific mechanism(s) proposed. Previous work in this and other models of hypertrophy suggest that changes in the number or activity of both Na(+)-K(+)-ATPase and Na(+)-Ca2+ exchange proteins are involved.

An increase in low aortic pressure increases coronary artery flow and coronary thrombolysis induced by intravenous administrarion of recombinant tissue plasminogen activator

Purpose: Our study investigated the effects of an increase in aortic pressure, induced by norepinephrine (NE) administration on coronary artery flow in a clotted artery, and rate of coronary thrombolysis induced by intravenous (IV) administration of recombinant tissue plasminogen activator (rtPA). Methods: A canine model of coronary thrombosis, induced by intracoronary injection of radioactive autologous blood clots, was used to test the hypothesis that an increase in aortic blood pressure will increase coronary artery flow and the rate of clot lysis induced by IV administration of rtPA. Results: After clot injection, 11 dogs were phlebotomized to decrease systolic aortic pressure to 75 mm Hg. Subsequently, .25 mg/kg of rtPA was administered intravenously over two 15-minute intervals, one during hypotension, and the other after NE infusion had increased systolic blood pressure to 130 mm Hg. In six dogs the hypotensive condition was studied first, and in five dogs the NE-induced normotensive condition was studied first. In all dogs, coronary artery flow and the rate of clot lysis were significantly increased in the normotensive condition. Conclusions: These results indicate that an increase in a low coronary artery perfusion pressure may enhance coronary artery flow and the rate of thrombolysis.

Diastolic function of the nonfilling human left ventricle

Objectives. To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice.Background. When mitral inflow was impeded in anesthetized dogs. left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect.Methods. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon.Results. The left ventricular diastolic asymptote pressure (Pasy) was determined in 47 nonfilling beats with a sufficiently long (>200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 ± 3 mm Hg for beats with normal intraventricular conduction and 3 ± 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 ± 14 ml and was comparable to the left ventricular end-systolic volume (39 ± 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval >200 ms, normal intraventricular conduction and peak left ventricular pressure >50 mm Hg. Time constants (Toand Tbf) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (Tasy) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for Tasy(37 ± 9 ms) was significantly smaller than that for Tbf(68 ± 28 ms, p < 0, 001) and the value for the measured diastolic left ventricular asymptote pressure (2 ± 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 ± 11 mm Hg, p < 0.001). To(44 ± 20 ms) was significantly (p < 0.01) different from Tbfbut not from Tasy.Conclusions. During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and towas a better measure of Tasythan was TbfReduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.

Influence of low perfusion pressure on effect of endothelin on coronary vascular bed

The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.

Nonuniform blood flow in the canine left ventricle

In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 ± 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 ± 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 ± 10%; P < 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.