Cardiac Oxygen Demand Research Articles

Review of cardiac-coronary interaction and insights from mathematical modeling.

Cardiac-coronary interaction is fundamental to the function of the heart. As one of the highest metabolic organs in the body, the cardiac oxygen demand is met by blood perfusion through the coronary vasculature. The coronary vasculature is largely embedded within the myocardial tissue which is continually contracting and hence squeezing the blood vessels. The myocardium-coronary vessel interaction is two-ways and complex. Here, we review the different types of cardiac-coronary interactions with a focus on insights gained from mathematical models. Specifically, we will consider the following: (1) myocardial-vessel mechanical interaction; (2) metabolic-flow interaction and regulation; (3) perfusion-contraction matching, and (4) chronic interactions between the myocardium and coronary vasculature. We also provide a discussion of the relevant experimental and clinical studies of different types of cardiac-coronary interactions. Finally, we highlight knowledge gaps, key challenges, and limitations of existing mathematical models along with future research directions to understand the unique myocardium-coronary coupling in the heart. This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Cardiovascular Diseases > Molecular and Cellular Physiology.

101 Differentiating Type 1 from Type 2 Acute Myocardial Infarction in the Emergency Department Using the N-terminal Pro B-type Natriuretic Peptide/High-sensitivity Cardiac Troponin T Ratio

Acute myocardial infarction (AMI) is currently further diagnosed as being a type 1 (T1), caused by coronary artery atherosclerosis with thrombosis or a type 2 (T2), resulting from cardiac oxygen supply and demand imbalance. It is hypothesized that patients with T2 might develop earlier and increased cardiac wall stressing before the development of AMI as compared to those with T1, resulting in higher N- terminal pro B-type natriuretic peptide (NT-proBNP)/high sensitivity cardiac troponin T (hs-cTnT) ratios.

The Effect of Acute Administration of the Aqueous Calyx Extract of Hibiscus sabdariffa on Blood pressure, Heart rate and Double Product of Apparently Healthy Human Subjects during Different Postures.

The aqueous calyx extract of Hibiscus sabdariffa (HS) is widely consumed as a beverage in Northern Nigeria and other parts of the world. HS has been reported to lower blood pressure (BP) in animals and man. However, not much is known about the effect of HS on BP in different postures. We tested the hypothesis that HS may lower BP, heart rate (HR) and heart rate-pressure product or double product (DP) by attenuating the discharge of the autonomic nervous system in different postures. Experiments were performed in accordance with the Principles of the Declaration of Helsinki. Following ethical approval and informed consent, BP and HR were measured in different postures (supine, sitting and standing) in apparently healthy human subjects (n=20) before and after (+HS) the oral administration of 15mg/Kg HS. Mean arterial pressure (MAP; taken as representative BP) and DP were calculated. Results are expressed as mean ±SEM. Paired t test and ANOVA with a post hoc Bonferroni test were used for statistical analyses. P<0.05 was considered significant. In the supine position MAP, HR and DP were significantly (P<0.0001 each) reduced in the presence of HS (85.6±1.7mmHg, 72.1±1.1/min and 8716±320mmHg.bpm) compared to its absence (89.6±2.0mmHg, 73.7±1.6/min and 8921±444mmHg.bpm). Similar trends were observed in the sitting position in the presence of HS (85.4±2.7mmHg, 73.7±1.8/min and 9098±345mmHg.bpm vs its absence: 91.4±2.3mmHg, 77.1±1.9/min and 9388±478mmHg.bpm; P<0.0001, P<0.0001 and P=0.007 respectively) and in the standing position (+HS: 89.3±2.0mmHg, 78.1±1.8/min and 10164±230mmHg.bpm vs its absence: 94.3±2.1mmHg, 81.8±2.3/min and 10742±268mmHg.bpm; P<0.0001, P<0.0001 and P=0.007 respectively). In the absence of HS, HR and DP were significantly higher in the standing posture (81.8±2.3/min, 10742±268mmHg.bpm) compared to the sitting (77.1±1.9/min, 9388±478mmHg.bpm; P<0.05 and P<0.0001 respectively) and the supine (73.7±1.6/min, 8921±444mmHg.bpm; P<0.001 each) postures while the BP remained similar. A similar trend was observed across the three postures in the presence of HS although the parameters were significantly lower. It is concluded that HS lowered BP, HR and DP by modulating autonomic mechanisms through the inhibition of both parasympathetic withdrawal and sympathetic nervous system discharge across the postures. Also the standing posture is associated more with a higher sympathetic nervous system discharge and a higher cardiac oxygen demand and workload than the sitting and supine postures in the absence or presence of HS.

Diuretic Activity of Indian Medicinal Plant: A Review

Diuretics are commonly defined as drugs that increase the amount of urine produced by kidney. A precise definition is that diuretics are the agent which augment the renal excretion of sodium and either chloride or bicarbonate primarily, and water excretion secondarily. The term “saluretic” is sometime used to describe a drug that increase the renal excretion of sodium and chloride ion Diuretics are responsible for increase the rate of urine flow, sodium excretion and to maintain the volume and composition of body fluids in a various clinical Disorders. But drug-induced diuresis is very much beneficial in such type of life-threatening disorders like CHF, hypertension, renal failure, Liver cirrhosis and often pregnancy toxaemia.[1] Diuretics relieve pulmonary congestion and peripheral edema. This decreases cardiac workload, oxygen demand and plasma volume, thus decreasing blood pressure. Thus, diuretics play an important role in hypertensive patients.[2] Plant medicine is commonly used in the traditional treatment of some renal diseases, and many plants are reported to possess significant diuretic activity. The diuretic activity of a number of plants used in ethno medicine as diuretic agents has been confirmed in experimental animal. [3]The progress of a polyherbal formulation is a tough job because of the large number of different chemical compounds present in the different medicinal plants.

Description of Visfatin Adipokine and its Roles on Inflammation and Coronary Heart Disease

Coronary heart disease (CHD) is a generic designation for a group of related syndromes resulting from myocardial ischemia – an imbalance between cardiac blood supply (perfusion) and myocardial oxygen demand. Visfatin (VF) is a recently discovered adipokine with different functions, Visfatin is mainly found in visceral adipose tissue and mimics insulin in lowering plasma glucose levels and, Visfatin emerges as a player in the development and progression of atherosclerotic lesions by directly promoting smooth muscle cell proliferation, Aberrant angiogenesis is now considered a feature of the atherogenic process in both coronary and carotid diseases. This adipokine was previously known as a pre-B-cell colony-enhancing factor (PBEF) or Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) an enzyme that in humans is encoded by the NAMPT gene and demonstrated to be an intracellular protein with a key enzyme role in nicotinamide adenine dinucleotide (NAD)

The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease- A Network Pharmacology and Proteomics Approach.

Yixin Ningshen tablet is a CFDA-approved TCM formula for treating coronary heart disease (CHD) clinically. However, its active compounds and mechanism of action in treating CHD are unknown. In this study, a novel strategy with the combination of network pharmacology and proteomics was proposed to identify the active components of Yixin Ningshen tablet and the mechanism by which they treat CHD. With the application of network pharmacology, 62 active compounds in Yixin Ningshen tablet were screened out by text mining, and their 313 potential target proteins were identified by a tool in SwissTargetPrediction. These data were integrated with known CHD-related proteomics results to predict the most possible targets, which reduced the 313 potential target proteins to 218. The STRING database was retrieved to find the enriched pathways and related diseases of these target proteins, which indicated that the Calcium, MAPK, PI3K-Akt, cAMP, Rap1, AGE-RAGE, Relaxin, HIF-1, Prolactin, Sphingolipid, Estrogen, IL-17, Jak-STAT signaling pathway, necroptosis, arachidonic acid metabolism, insulin resistance, endocrine resistance, and steroid hormone biosynthesis might be the main pathways regulated by Yixin Ningshen tablet for the treatment of CHD. Through further enrichment analysis and literature study, EGFR, ERBB2, VGFR2, FGF1, ESR1, LOX15, PGH2, HMDH, ADRB1, and ADRB2 were selected and then validated to be the target proteins of Yixin Ningshen tablet by molecular docking, which indicated that Yixin Ningshen tablet might treat CHD mainly through promoting heart regeneration, new vessels' formation, and the blood supply of the myocardial region and reducing cardiac output, oxygen demand, and inflammation as well as arteriosclerosis (promoting vasodilation and intraplaque neoangiogenesis, lowering blood lipid). This study is expected to benefit the clinical application of Yixin Ningshen tablet for the treatment of CHD.

Extracorporeal Life Support Enhances the Forward Pressure Wave to Cause a Mismatch between Cardiac Oxygen Demand and Supply

Extracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone. Ascending aortic pressure signals were measured before ECLS and at 30, 60, and 90 min after weaned off. The aortic pressure signal then calculated by fourth-order derivative to obtain an assumed triangular flow wave. The ratio of mean systolic pressure to mean diastolic pressure (Pms/Pmd), a parameter for evaluating the matching condition between myocardial oxygen demand and supply, was significantly higher after ECLS. The magnitude of forward pressure (|Pf|) augmented by ECLS prevailed over the backward pressure (|Pb|), leading to a decline in wave reflection factor. Pms/Pmd was positively linearly correlated with |Pf| (Pms/Pmd = 0.9177 + 0.0078 × |Pf|, r = 0.8677; P < 0.0001). These findings suggest that |Pf| was a predominant factor responsible for the mismatch between the myocardial oxygen demand and supply in rats after ECLS phase of experiment.

Stable coronary artery disease: are there therapeutic benefits of heart rate lowering?

: A physiologically lower heart rate, such as that seen in athletes, has been associated with better survival in epidemiological studies. In patients with coronary artery disease, heart rate is considered an independent risk factor for adverse outcomes. Higher heart rate increases cardiac work load and oxygen demand and reduces coronary perfusion by decreasing the amount of time spent in diastole, which in patients with obstructive coronary artery disease can trigger angina and myocardial infarction. Whether pharmacological reduction in heart rate by using a beta-blocker or ivabradine improves prognosis has been debated. In this review, we explore the effect of pharmacological heart rate lowering with a beta-blocker or ivabradine on cardiovascular outcomes in patients with cardiovascular disease and address the question as to whether pharmacological heart rate reduction is ready for prime time in the management of patients with coronary artery disease. Although physiologically lower heart rates are associated with improved survival, the effect of pharmacological heart rate reduction with beta-blockers (in patients without heart failure or postmyocardial infarction) or ivabradine on improvement in survival is weak at best.

A CASE OF BIGEMINY AND SUCCESSFUL COMPLETION OF ACUTE ELECTROCONVULSIVE THERAPY COURSE

Introduction Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community due to misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Several concerns have risen regarding the safety of ECT on the cardiovascular system. ECT causes periprocedural hemodynamic variability due to the surges in parasympathetic and sympathetic nervous systems following the administration of the electric current.1 Patients experience an increase in cardiac workload and oxygen demand, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest the incidence of cardiac complications is relatively rare and occurs most frequently in patients with underlying cardiovascular disease. Methods We describe a case report of a 53 year old female with history of bipolar I disorder current episode depressed, hyperlipidemia undergoing ECT who developed cardiovascular complications after her seventh brief pulse right unilateral (BRUL) treatment. Electrocardiogram (EKG) monitoring revealed bigeminy for two to three minutes (heart rate in 80s) during post-anesthesia care. Results The cardiovascular system undergoes various changes during ECT including events secondary to the parasympathetic release such as asystole, hypotension, bradycardia, and events secondary to sympathetic release such as hypertension and tachycardia. Other complications include arrhythmias, ST elevation, and Takotsubo Cardiomyopathy. The patient was seen by cardiology for further work-up. EKG, 2-D cardiac echocardiogram, 48-hour Holter monitoring, and coronary CT calcium scan were performed. She was found to have rare premature atrial contractions (PACs) (8 in 48 hours). Her bigeminy resolved spontaneously. The patient was able to complete the acute course of BRUL ECT and continued onto maintenance ECT with good effect. We also present a table with the common cardiovascular side effects from ECT and the most recent evidence-based treatment strategies to manage them. Conclusions Generally, ECT is a safe procedure; complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary-team approach the cardiovascular complications can be well managed and minimized. Our case highlights the benefits of a multidisciplinary care model between psychiatry, anesthesia, and cardiology. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide. This research was funded by None.

Effect of Laparoscopic Ovarian Drilling on Anti-Müllerian Hormone Level among Women with Polycystic Ovary Syndrome : A Retrospective Study

Background: Thyroid dysfunction is associated with increased cardiovascular morbidity and mortality. Hyperthyroidism increases the susceptibility of the heart to ischemia reperfusion injury. Moreover, myocardial ischemia can be further worsened by increased cardiac workload and oxygen demand elicited by the excess thyroid hormones. Objectives: Investigating the cardiac dysfunction induced by ischemia-reperfusion (IR) in rats exposed to excess thyroid hormones and role of somatostatin analogue against ischemia/reperfusion injury in hyperthyroid rats. Patients and Methods: This study was performed on 24 adult male albino rats of a local strain weighing 140-200 g, allocated into three equal groups: Group I (Control IR group): Euthyroid control group exposed to ischemia-reperfusion. Hearts of this group were isolated and perfused in a Langendorff apparatus. Isolated hearts were subjected to 15 min of stabilization, 20 min of zero-flow global ischemia and 30 min of reperfusion. Group II (Hyperthyroid IR group) were subjected to the same protocol of ischemia reperfusion. Group III (Hyperthyroid IR-OCT group): Hyperthyroid rats were supplemented with the somatostatin analogue, octreotide (OCT), 35 µg/kg subcutaneously, 20 minutes before sacrifice, followed by in-vitro study of cardiac responses to ischemia reperfusion. Blood samples were collected for measurement of plasma free T3, T4 and TSH. Coronary efflux lactate dehydrogenase levels were measured. Also, cardiac tissue malondialdehyde (MDA) levels and tumor necrosis factor alpha (TNF-α) levels were estimated. Results: Hyperthyroid (IR) rats revealed significant elevation in plasma free T3 and T4 with concomitant decrease in TSH levels. A significant reduction in final BW and BW gain were observed with higher absolute weights of left ventricle (LV) and cardiac index compared to the euthyroid controls. Systolic blood pressure (SBP) and mean arterial pressure (MAP) significantly elevated in non-treated hyperthyroid rats with a significant increase in their baseline chronotropic and inotropic activity compared to euthyroid control rats. But after ischemia those rats exhibited significantly higher degree of bradycardia (∆HR) and % change in heart rate (HR) compared to control rats. Moreover, significantly deteriorated post-ischemic recovery of inotropic parameters and significantly higher ∆ changes of these parameters were observed compared to euthyroid controls. These changes were accompanied by significant elevation in coronary efflux LDH levels and both cardiac tissue MDA and TNFα. Meanwhile, octreotide administration to hyperthyroid rats showed improvement of their baseline chronotropic and inotropic parameters as evidenced by the significantly reduced degree of bradycardia as well as significantly lower ∆ change of PT and PT/LV parameters compared to non-treated hyperthyroid rats. Such findings could be ascribed partly to the reduction of oxidative and inflammatory responses to IR as determined by the significantly decreased cardiac tissue MDA and TNFα respectively. Conclusion: Hyperthyroid hearts are less tolerant to ischemia/reperfusion injury with higher susceptibility to oxidative stress as well as overproduction of pro-inflammatory mediators. Thus, pharmacological targets that defend oxidative challenge and confer anti-inflammatory properties, namely octreotide (somatotstatin analogue) are considered to have potential therapeutic effect and may protect against myocardial ischemic damage in hyperthyroidism.

Cardiac Chemoreflex Control of Cardiac Stroke Work and Energy Consumption

The activation of cardiac chemosensitive receptors elicit the Bezold‐Jarish reflex, which triggers parasympathetic activity and inhibits sympathetic activity, resulting in bradycardia and decreased arterial pressure. This is a cardioprotective reflex, strongly amplified by products of acute myocardial ischemia and its effect has been extensively evaluated on heart rate and arterial pressure. Cardiac stroke work and total energy consumption are tightly regulated and we hypothesized that the Bezold‐Jarish reflex can participate in this regulation.In anesthetized, paralyzed and artificially ventilated rabbits the Bezold‐Jarish reflex was evoked by cardiac injection of ATP. An intraventricuar impedance catheter was used to measure simultaneously ventricular pressure and volume. All experiments were performed according to national laws and international guidelines.We employed this pressure‐volume framework to characterize left ventricular and arterial physiologic properties. We designed a custom software to compute single beat left ventricle end‐systolic elastance (Ees), arterial elastance (Ea) and their ratio (Ees/Ea) to analyze ventriculo‐arterial coupling. From this data we calculated left ventricular stroke work (SW), total energy expenditure (PVA), ratio of the SW to its theoretical maximum (Qload) and energetic efficiency (Eff=SW/PVA).Statistical analysis with paired Student's t‐test of our results (Table 1) show a significant increase in Ees and a non significant decrease in Ea, without a major change in their coupling ratio (Ees/Ea). This resulted in a significant decrease in both SW and PVA with such a balance that Qload and Eff remained unchanged.These results indicate that the Bezold‐Jarish reflex participates in the regulation of the cardiac SW and PVA in a protective way that decreases oxygen demand. In fact previous work has shown that PVA is proporcional to total cardiac oxygen demand. This regulation of cardiac work and total energy consumption by the Bezold‐Jarish reflex may protect the heart during ischemia. This protective decrease in SW and PVA by the Bezold Jarish is obtained without sacrifice of the energetic efficicency of the heart.Support or Funding InformationEXCL/MAT‐NAN/0114/2012; Physiomat ‐ Fundacao Ciencia Tecnologia Mean and standard deviation of cardiac variables before and after injection, and p‐values from paired Student's t‐test. baseline (20 beats) after injection (20 beats) p‐value (t‐test) Arterial pressure (mmHg) 72 ± 0,56 62 ± 5,75 0,0004 Instantaneous Heart Rate (bpm) 233 ± 1,17 222 ± 3,30 0,2 Arterial elastance (Ea) (mmHg/mL) 2,44 ± 0,17 2,89 ± 0,55 0,3 End‐systolic elastance (Ees) (mmHg/mL) 1,91 ± 0,13 1,668 ± 0,10 0,04 Ees / Ea 0,79 ± 0,07 0,60 ± 0,13 0,1 Ejection fraction (EF) (%) 0,47 ± 0,01 0,38 ± 0,02 0,03 Stroke volume (SV) (mL) 49,25 ± 1,31 37,59 ± 1,23 0,02 Stroke work (SW) (mmHg*mL) 4858 ± 144,84 3280 ± 225,85 0,002 Total energy expenditure (PVA) (mmHg*mL) 7579 ± 534,48 5672 ± 772,19 0,00006 Stroke work to its maximum (Qload) 0,91 ± 0,02 0,m85 ± 0,03 0,1 Heart efficiency (Eff) (%) 64 ± 1,93 56 ± 4,10 0,1

Cardiac oxygen supply is compromised during the night in hypertensive patients

The enhanced heart rate and blood pressure soon after awaking increases cardiac oxygen demand, and has been associated with the high incidence of acute myocardial infarction in the morning. The behavior of cardiac oxygen supply is unknown. We hypothesized that oxygen supply decreases in the morning and to that purpose investigated cardiac oxygen demand and oxygen supply at night and after awaking. We compared hypertensive to normotensive subjects and furthermore assessed whether pressures measured non-invasively and intra-arterially give similar results. Aortic pressure was reconstructed from 24-h intra-brachial and simultaneously obtained non-invasive finger pressure in 14 hypertensives and 8 normotensives. Supply was assessed by Diastolic Time Fraction (DTF, ratio of diastolic and heart period), demand by Rate-Pressure Product (RPP, systolic pressure times heart rate, HR) and supply/demand ratio by A dia/A sys, with A dia and A sys diastolic and systolic areas under the aortic pressure curve. Hypertensives had lower supply by DTF and higher demand by RPP than normotensives during the night. DTF decreased and RPP increased in both groups after awaking. The DTF of hypertensives decreased less becoming similar to the DTF of normotensives in the morning; the RPP remained higher. A dia/A sys followed the pattern of DTF. Findings from invasively and non-invasively determined pressure were similar. The cardiac oxygen supply/demand ratio in hypertensive patients is lower than in normotensives at night. With a smaller night-day differences, the hypertensives’ risk for cardiovascular events may be more evenly spread over the 24 h. This information can be obtained noninvasively.

Muscle metaboreflex-induced coronary vasoconstriction functionally limits increases in ventricular contractility

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility, and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. The purpose of the present study is to determine whether the restraint of coronary vasodilation functionally limits increases in left ventricular contractility. Using chronically instrumented, conscious dogs (n = 9), we measured mean arterial pressure, cardiac output, and circumflex blood flow and calculated coronary vascular conductance, maximal derivative of ventricular pressure (dp/dt(max)), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2 mph) before and during activation of the muscle metaboreflex. Experiments were repeated after systemic alpha(1)-adrenergic blockade ( approximately 50 microg/kg prazosin). During prazosin administration, we observed significantly greater increases in coronary vascular conductance (0.64 + or - 0.06 vs. 0.46 + or - 0.03 ml x min(-1) x mmHg(-1); P < 0.05), circumflex blood flow (77.9 + or - 6.6 vs. 63.0 + or - 4.5 ml/min; P < 0.05), cardiac output (7.38 + or - 0.52 vs. 6.02 + or - 0.42 l/min; P < 0.05), dP/dt(max) (5,449 + or - 339 vs. 3,888 + or - 243 mmHg/s; P < 0.05), and PRSW (160.1 + or - 10.3 vs. 183.8 + or - 9.2 erg.10(3)/ml; P < 0.05) with metaboreflex activation vs. those seen in control experiments. We conclude that the sympathetic restraint of coronary vasodilation functionally limits further reflex increases in left ventricular contractility.

Potential association between aortic stiffness, diastolic/systolic pressure time index and the balance between cardiac oxygen supply and demand: a word of caution

Potential association between aortic stiffness, diastolic/systolic pressure time index and the balance between cardiac oxygen supply and demand: a word of caution

Potential association between aortic stiffness, diastolic/systolic pressure time index and the balance between cardiac oxygen supply and demand: a word of caution

Potential association between aortic stiffness, diastolic/systolic pressure time index and the balance between cardiac oxygen supply and demand: a word of caution

Aortic stiffness and the balance between cardiac oxygen supply and demand: the Rotterdam Study

Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality. We investigated whether aortic stiffness, estimated as aortic pulse wave velocity, is associated with decreased perfusion pressure estimated as the cardiac oxygen supply potential. Aortic stiffness and aortic pressure waves, reconstructed from finger blood pressure waves, were obtained in 2490 older adults within the framework of the Rotterdam Study, a large population-based study. Cardiac oxygen supply and demand were estimated using pulse wave analysis techniques, and related to aortic stiffness by linear regression analyses after adjustment for age, sex, mean arterial pressure and heart rate. Cardiac oxygen demand, estimated as the Systolic Pressure Time Index and the Rate Pressure Product, increased with increasing aortic stiffness [0.27 mmHg s (95% confidence interval: 0.21; 0.34)] and [42.2 mmHg/min (95% confidence interval: 34.1; 50.3)], respectively. Cardiac oxygen supply potential estimated as the Diastolic Pressure Time Index decreased [-0.70 mmHg s (95% confidence interval: -0.86; -0.54)] with aortic stiffening. Accordingly, the supply/demand ratio Diastolic Pressure Time Index/Systolic Pressure Time Index -1.11 (95% confidence interval: -0.14; -0.009) decreased with increasing aortic stiffness. Aortic stiffness is associated with estimates of increased cardiac oxygen demand and a decreased cardiac oxygen supply potential. These results may offer additional explanation for the relation between aortic stiffness and cardiovascular morbidity and mortality.

Muscle Metaboreflex Control of Coronary Blood Flow and Ventricular Contractility During Dynamic Exercise

Muscle metaboreflex activation (MMA) during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility and afterload. This increase in cardiac work should lead to coronary metabolic vasodilation. However, in this situation, little if any coronary vasodilation is observed. It is unclear if this lack of coronary vasodilation, which occurs as a result of increased coronary sympathetic stimulation due to MMA, suppresses any further increases in left ventricular contractility (LVC). The purpose of this study was to determine if this lack of coronary vasodilation leads to a buffered increase in LVC. Using chronically instrumented, conscious dogs we measured arterial pressure, cardiac output (CO), circumflex blood flow (CxBF), and calculated coronary vascular conductance (CVC), maximal derivative of ventricular pressure (dp/dt), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2mph) before and after MMA. Experiments were repeated after alpha-1 adrenergic blockade (prazosin ∼50 ìg/kg). During prazosin we observed significantly greater increases in CVC, CxBF, CO, dP/dt, and PRSW, with MMA, over that of the control condition. We conclude that the lack of coronary vasodilation limits further improvement in LVC. NIH HL 55473

Tribute to P. L. Lutz: a message from the heart – why hypoxic bradycardia in fishes?

The sensing and processing of hypoxic signals, the responses to these signals and the modulation of these responses by other physical and physiological factors are an immense topic filled with numerous novel and exciting discoveries. Nestled among these discoveries, and in contrast to mammals, is the unusual cardiac response of many fish to environmental hypoxia - a reflex slowing of heart rate. The afferent and efferent arms of this reflex have been characterised, but the benefits of the hypoxic bradycardia remain enigmatic since equivocal results have emerged from experiments examining the benefit to oxygen transfer across the gills. The main thesis developed here is that hypoxic bradycardia could afford a number of direct benefits to the fish heart, largely because the oxygen supply to the spongy myocardium is precarious (i.e. it is determined primarily by the partial pressure of oxygen in venous blood, Pv(O(2))) and, secondarily, because the fish heart has an unusual ability to produce large increases in cardiac stroke volume (V(SH)) that allow cardiac output to be maintained during hypoxic bradycardia. Among the putative benefits of hypoxic bradycardia is an increase in the diastolic residence time of blood in the lumen of the heart, which offers an advantage of increased time for diffusion, and improved cardiac contractility through the negative force-frequency effect. The increase in V(SH) will stretch the cardiac chambers, potentially reducing the diffusion distance for oxygen. Hypoxic bradycardia could also reduce cardiac oxygen demand by reducing cardiac dP/dt and cardiac power output, something that could be masked at cold temperature because of a reduced myocardial work load. While the presence of a coronary circulation in certain fishes decreases the reliance of the heart on Pv(O(2)), hypoxic bradycardia could still benefit oxygen delivery via an extended diastolic period during which peak coronary blood flow occurs. The notable absence of hypoxic bradycardia among fishes that breathe air during aquatic hypoxia and thereby raise their Pv(O(2)), opens the possibility that that the evolutionary loss of hypoxic bradycardia may have coincided with some forms of air breathing in fishes. Experiments are needed to test some of these possibilities. Ultimately, any potential benefit of hypoxic bradycardia must be placed in the proper context of myocardial oxygen supply and demand, and must consider the ability of the fish heart to support its routine cardiac power output through glycolysis.

Comment on "Survival Pattern in Patients with Acute Organophosphate Poisoning Receiving Intensive Care"

To the Editor: Munidasa et al. observed that refractory hypotension was strongly associated with a high early mortality from organophosphate poisoning despite adequate respiratory support, inotropes, and intensive care (1). The authors speculated that the most likely mechanism was globally impaired myocardial function as these patients typically also had pulmonary oedema. However other smaller series of similar patients with invasive monitoring suggest other mechanisms may be important. We and others have found extremely low vascular resistance in OP poisoned patients with hypotension refractory to catecholamines (2 – 4). Despite the patients being clinically atropinised the low vascular resistence responded partially to very high doses of atropine but not to other vasopressors. We postulated that this vasodilation was due to stimulation of the vascular endothelial muscarinic receptor resulting in the release of nitric oxide (2). We have observed this repeatedly in subsequent patients, and the hypotension in most patients is usually associated with a high rather than a low cardiac output (similar to septic shock) (2 – 4). There are a number of other mechanisms that may contribute to hypotension in organophosphate poisoning. Despite causing generalized vasodilation, acetylcholine can also induce vasoconstriction at sites where the endothelium is damaged (5), and this might lead to myocardial ischemia. Cardiac oxygen demand may be higher, due to the high cardiac output state and excessive endogenous or exogenous catecholamines. As well as contributing to focal ischemia, this could lead to diffuse myocardial necrosis similar to that seen with phaeochromocytoma (6,7). In addition there may be diffuse endothelial injury or cardiotoxicity from reactive oxygen species (8) or cardiac effects may be secondary to acidosis or electrolyte abnormalities (9), and others have speculated that the hypotension may be centrally mediated (3), although generally central cholinesterase inhibition leads to a pressor response (10). We agree with Munidasa et al.’s implication that refractory hypotension is the leading cause of death in anticholinesterase poisonings that are receiving maximal supportive care. It is plausible that one, many or all of these different mechanisms are important. A rational approach to the management of patients with refractory hypotension depends on the development of a much better understanding of the pathophysiology. Only then will it be clearer what treatment options are appropriate, what investigations are required, and whether treatment needs to be individualized or if clinical trials of antidotes for the hypotension are feasible.

Coronary vascular dysfunction in premenopausal women with diabetes mellitus

Background Diabetes mellitus abolishes the sex differential in coronary artery disease morbidity and mortality in premenopausal women. This finding is independent of other diabetes-associated risk factors, suggesting that other mechanisms such as impaired coronary vascular function may contribute to the increased cardiovascular risk in women with diabetes. The objective of this study was to investigate the effect of diabetes on coronary vascular function in premenopausal women. Methods We studied 13 premenopausal women with diabetes (aged 41 ± 10 years) who were free of overt cardiovascular complications, and 21 control women (12 age-matched and 9 postmenopausal [aged 56 ± 8 years]). We used [13N]-ammonia as the flow tracer and positron emission testing to measure myocardial blood flow (MBF) at rest, during maximal hyperemia, and in response to cold pressor testing. Results Baseline MBF was lower in the postmenopausal controls, reflecting the differences in cardiac work and oxygen demand as assessed by the rate-pressure product. However, baseline MBFs were similar in the 3 groups after normalization for differences in the rate-pressure product. During hyperemia, MBF increased and coronary vascular resistance decreased significantly in the 3 groups. However, the increase (from baseline) in MBF in the women with diabetes (164% ± 58%) was less than in the premenopausal controls (258% ± 81%, P =.021), but not significantly different from the postmenopausal control women (204% ± 104%, P =.51). Likewise, the increase in MBF in response to cold pressor testing in the women with diabetes (24% ± 19%) was significantly lower than in the premenopausal controls (60% ± 39%, P =.013), but similar to that in postmenopausal control women (27% ± 15%, P =.97). These differences persisted after adjusting for age and diabetes-associated metabolic abnormalities. Conclusions These results demonstrate reduced coronary vasodilator function and impaired response of resistance vessels to increased sympathetic stimulation in premenopausal women with diabetes, similar to those observed in healthy postmenopausal women in whom the sex differential in coronary artery disease morbidity and mortality is no longer present. (Am Heart J 2002;144:711-8.)