Biomedical subjects

Christian Korvald

Publications and source records attributed to Christian Korvald.

10 recordsLinked to original sources

PubMed2006

The pressure-volume loop revisited: Is the search for a cardiac contractility index a futile cycle?

UNLABELLED: Our previous studies indicate that left ventricular end-systolic pressure-volume relations (ESPVRs) or elastance (Ees) are not reduced in studies where expected reductions of contractility should be found (i.e., heart failure, stunning, and endotoxemia). The present study was done to assess whether this phenomenon is due to a particular load sensitivity of elastance, rendering this index inappropriate as a measurement of contractility in pathologic states in vivo. METHODS AND RESULTS: Analysis of previously generated data revealed an increased ESPVR in stunned hearts, in pigs made endotoxemic, and in hearts rapidly paced. After inducing acute heart failure by microembolization, the ESPVR was increased when assessed using linear relations but reduced when assessing ESPVR by a curvilinear algorithm. To further evaluate the effect of different load alterations on ESPVR, this relation was generated by (i) inferior vena caval occlusions (VCOs); (ii) gradually occluding the descending aorta (pressure interventions); and (iii) rapidly infusing blood (120 mL) into the left atrium (volume increments). The load protocol was applied in 5 pigs, before and after the left ventricle was stunned by 11 brief left main coronary artery occlusions/reperfusions (accumulated ischemia 20 min affecting 81% of the left ventricle). Correlation coefficients for left ventricular elastance ranged from 0.93 to 0.99 in all the 3 types of loading interventions. Despite significant reductions in stroke volume, stroke work, and dP/dtmax, VCO-calculated linear and curvilinear Ees increased 90 min after stunning (55% +/- 4% and 94% +/- 6%, respectively). Linear Ees during pressure interventions decreased 36% +/- 1%, whereas curvilinear Ees decreased 33% +/- 3%. During volume infusions, linear Ees decreased 27% +/- 2%. We achieved the same results after blocking the baroreceptor reflexes using hexamethonium. CONCLUSIONS: The Ees is particularly load dependent and will reflect load interventions more than the inotropic state of the cardiac muscle. A VCO-generated Ees increase could be an unmasking of a pronounced preload sensitivity in failing myocardium.

Animals↗

PubMed2005

Mechanical restitution curves reflect post-ischemic stunning in pigs.

OBJECTIVES: The time constant of mechanical restitution (T(MRC)), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure. In this study, we tested the hypothesis that T(MRC) also can identify post-ischemic, reversible LV dysfunction (stunning). DESIGN: Stunning was induced by a series of left main coronary artery occlusions in eight anesthetized open chest pigs. Left ventricular pressure-volume relations were assessed using a pressure-volume catheter during right atrial pacing. Mechanical restitution curves (MRCs) were constructed using two different measures of contractile response: maximal first derivative of pressure (CR(dP/dtmax)) and stroke work (CR(SW)). RESULTS: Mean arterial pressure, stroke volume and dP/dtmax were decreased 30 min after stunning. Slopes of end-systolic pressure volume relation and preload recruitable stroke work, however, showed no significant changes after stunning. For MRCs based on CR(dP/dtmax), T(MRC) increased in all eight animals. Using CR(SW), T(MRC) increased in seven out of eight pigs. CONCLUSIONS: Ischemia-reperfusion induce changes in MRCs based on CR(dP/dtmax), and CR(SW). The MRC concept may have potential as a clinical left ventricular performance index.

Animals↗

PubMed2004

Mechanoenergetic inefficiency in the septic left ventricle is due to enhanced oxygen requirements for excitation-contraction coupling.

OBJECTIVE: Myocardial oxygen consumption (MVO2) in the septic myocardium is increased despite reduced left ventricular mechanical work. We investigated the mechanism behind this energetic inefficiency in the septic myocardium. METHODS: To clarify whether energy consumption in basal metabolism or excitation-contraction (EC) coupling is elevated in the septic myocardium, we separated MVO2 used for these two processes. We assessed hemodynamics, left ventricular pressure-volume area, left ventricular MVO2, myocardial substrate metabolism and the inflammatory response in eight control pigs and in eight septic pigs receiving E. coli endotoxin. Using cardiopulmonary bypass (CPB), unloaded MVO2 was assessed before and after arrest of electromechanical activity using KCl infusions. RESULTS: Unloaded MVO2 was significantly higher in the septic group compared to the control group (65.7 +/- 12.9 vs. 43.3 +/- 15.1 J.min(-1).100 g LV(-1), p < 0.005), but basal MVO2 after 5 min KCl arrest was equal in the two groups. No difference in mechanical energy consumption or substrate metabolism was observed between groups. CONCLUSION: Basal MVO2 in the septic myocardium is not elevated, but an increased MVO2 for EC coupling is responsible for the energetic inefficiency.

Animals↗

PubMed2004

Nitric oxide synthase inhibition impairs myocardial efficiency and ventriculo-arterial matching in acute ischemic heart failure.

BACKGROUND AND AIMS: The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. METHODS: Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). RESULTS: Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). CONCLUSION: Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.

Animals↗

PubMed2004

Increased oxygen cost of contractility in the endotoxemic porcine left ventricle.

OBJECTIVE: Myocardial oxygen consumption (MVO) in the septic myocardium is comparatively high in relation to the sepsis-induced reduction in ventricular work. Our previous studies indicate that this energetic inefficiency is due to increased energy consumption in excitation-contraction (EC) coupling, i.e. myocardial calcium handling. DESIGN: To further confirm this observation, we assessed the oxygen cost of contractility in anesthetized pigs before and 2 h after induction of endotoxemia (1 microg/kg endotoxin infusion over 1 h, Escherichia coli toxin, n=6). Baroreceptor reflexes were blocked by hexamethonium. Contractility was increased by stepwise dopamine infusions at baseline and 2 h after induction of endotoxemia. Oxygen cost of contractility was assessed as the relationship between myocardial contractility (E or elastance) and non-mechanical oxygen consumption (unloaded MVO), a measure of energy consumption in EC coupling or calcium handling. RESULTS: Non-mechanical oxygen consumption (unloaded MVO) was higher after endotoxin infusions than at baseline (0.641 +/- 0.05 vs 0.383 +/- 0.07 J/beat/100 g, p < 0.05). The relationship between unloaded MVO and E, constructed by the dopamine response, was highly linear both at baseline and endotoxemia (r2 =0.76-0.99). However, endotoxin increased oxygen cost of contractility by approximately 45% (baseline 0.06 +/- 0.03 vs endotoxin 0.09 +/- 0.04 J ml/mmHg/beat/100 g). CONCLUSION: Acute endotoxemia increases oxygen cost of contractility, a measure of energy consumed in EC coupling or myocardial calcium handling.

Animal Experimentation↗

PubMed2004

E. Coli sepsis induces profound mechanoenergetic inefficiency in the porcine left ventricle.

Myocardial dysfunction is believed to be a central part of septic multiorgan manifestations. The aim of the present study was to assess whether E. coli sepsis in an in vivo model would induce a dysfunction in the relationship between mechanical work and energy consumption in the left ventricle (LV). Accordingly, we measured hemodynamics, left ventricular pressure-volume area (PVA), and myocardial oxygen consumption (MVo2) in deeply anesthetized pigs. Eight pigs received 2.0 +/- 0.5 x 10(9) E. coli bacteria intravenously, and seven served as controls. Compared with baseline and the control group, no alternations were observed in LV diastolic function or indices of contractility in the septic group. The MVo2-PVA relationship was highly linear in both groups (all r2 = 0.96-0.99). At 5 h, the y-axis intercept of the MVo2-PVA relationship (nonmechanical MVo2) had increased in the sepsis group by 70% compared with baseline (P = 0.004) and by 60% compared with the control group (P = 0.003). Contractile efficiency (the inverse of the MVo2-PVA slope) remained unchanged over time and between groups. The study demonstrates a profound increase in nonmechanical oxygen consumption during E. coli sepsis in the LV.

Animals↗

PubMed2002

Warm retrograde blood cardioplegia saves more ischemic myocardium but may cause a functional impairment compared to cold crystalloid.

OBJECTIVES: Ongoing ischemia, or even ischemia in progress, is regularly encountered in today's patients amenable to cardiac surgery. We set out to assess the effect of 'active resuscitation' during cardioplegia with warm continuous retrograde blood cardioplegia (WB) in a protocol simulating a clinical situation. METHODS: After 60 min with a regional ischemic injury to the left ventricle, 21 pigs were randomized to receive no treatment (control), cold retrograde intermittent crystalloid cardioplegia (CC) or WB. All animals were put on cardiopulmonary bypass. After 1h of cardioplegia and 1 h of reperfusion the perfused left ventricle was colored with methylene blue. After excision of the hearts a standard planimetri technique was used to determine the area at risk and amount of necrosis (triphenyltetrazolium). Heart rate, mean arterial pressure (MAP), cardiac output and myocardial blood flow were recorded as well as myocardial oxygen consumption, plasma levels of free fatty acids, glucose, lactate and Troponin T from the coronary sinus. RESULTS: The area at risk of the left ventricle was 13.6+/-1.2%. We found 71+/-2, 61+/-3 and 30+/-2% necrosis of the area at risk in the controls, CC and WB, respectively (P<0.001, CC versus control and P<0.0001, WB against CC and control). Troponin T release was highest in the CC group in the reperfusion period. Glucose levels increased significantly after ischemia in the controls and WB. In accordance with the amount of saved myocardium in the WB group which also had a normal coronary sinus lactate level as opposed to the fourfold increase in the CC group after ischemia. After standstill cardiac output and MAP were significantly lower than baseline values in the WB group only (P<0.05). CONCLUSIONS: CC did reduce the size of the infarction by about 10% compared to control animals, whereas WB reduced the infarction by more than 50% of that seen after CC. Both modalities are, however, associated with a functional reduction during the first 60 min of reperfusion, WB being the worst.

Animals↗

PubMed2002

Both glucose-insulin-potassium and glutamine in warm blood cardioplegia increase the rates of myocardial glucose and free fatty acid oxidation.

OBJECTIVE: We wanted to assess the effect of glucose-insulin-potassium (GIK) and glutamine on the oxidative metabolism during and after prolonged warm continuous blood cardioplegia (WB). DESIGN: WB was given to 21 pigs divided into three equally sized groups: WB (control), WB and GIK, or WB and glutamine. Oxidation rates of radiolabeled glucose (14C) and free fatty acid (FFA) (3H) were assessed before, during, and at 30 and 60 min after 3 h of cardiac arrest with WB. RESULTS: During standstill the substrate oxidation dropped markedly (<60%), glucose oxidation was highest in the WB + GIK group (p < 0.05) and FFA oxidation highest in the WB + glutamine group (NS). During recovery the GIK group had an elevated glucose oxidation (47 and 40% vs WB at 30 and 60 min recovery, respectively -p < 0.05). Following 30 min recovery the addition of GIK suppressed FFA oxidation some 60%. Glutamine increased the oxidation of both glucose (30%) and FFA (150%) following 60 min recovery (p < 0.05). During the whole recovery phase the relative FFA oxidation was significantly lowered in the GIK group. There were no differences between the groups regarding arterial levels or uptake of substrates, except for a higher myocardial oxygen consumption (MVO2) during cardioplegia in the glutamine group. All the hearts performed similarly. CONCLUSION: Addition of GIK or glutamine to the well-perfused and oxygenated heart during WB led to a postcardioplegic increase in oxidative metabolism and MVO2. GIK resulted in a significant metabolic shift from FFA to glucose.

Animals↗

PubMed2002

Pressure-volume-based single-beat estimations cannot predict left ventricular contractility in vivo.

The end-systolic pressure-volume relationship is regarded as a useful index for assessing the contractile state of the heart. However, the need for preload alterations has been a serious limitation to its clinical applications, and there have been numerous attempts to develop a method for calculating contractility based on one single pressure-volume loop. We have evaluated four of these methods. Pressure-volume data were obtained by combined pressure and conductance catheters in 37 pigs. All four methods were applied to 88 steady-state pressure-volume files, including eight files sampled during dopamine infusions. Estimates of single-beat contractility (elastance) were compared with preload-varied multiple-beat elastance [E(es(MB))]. All methods had a low average bias (-0.3 to 0.5 mmHg/ml) but limits of agreement (+/-2 SD) were unacceptably high (+/-2.6 to +/-3.8 mmHg/ml). In the dopamine group, E(es(MB)) showed an increase of 1.7 +/- 0.8 mmHg/ml (mean +/- SD) compared with baseline (P < 0.001). None of the single-beat methods predicted this increase in contractility. It is therefore doubtful whether any of the methods allow for single-beat assessment of contractility.

Animals↗

PubMed2002

Vasodilation and mechanoenergetic inefficiency dominates the effect of the "Ca(2+)-sensitizer" MCI-154 in intact pigs.

OBJECTIVE: Ca(2+)-sensitizing agents hold potential as ideal cardiac inotropes, but effects in intact animals are scarcely described. We evaluated a pyridazinone derivative, MCI-154, for hemodynamic, inotropic, mechanoenergetic and oxidative metabolic effects. DESIGN: Intracavitary left ventricular (LV) pressure and conductance (volume) was assessed in open chest anesthetized pigs (n = 6). Contractile performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were assessed. Myocardial substrate uptake and production of (14)CO(2 )(from glucose) and (3)H(2)O (from fatty acids) were monitored. MCI-154 administration: "low range": 0.1, 0.2, 0.3, 0.5 microg/kg/min and "high range": 0.75, 1.0, 2.0, 3.0 microg/kg/min. Parameters were compared with baseline and a time reference group (n = 7). RESULTS: MCI-154 induced a progressive dose-dependent decrease in systemic vascular resistance, with a concomitant increase in heart rate and cardiac output. Contractility increased only in the high-dose range, and mechanoenergetic efficiency was significantly reduced by drug infusion in all doses. CONCLUSION: The pyridazinone derivative MCI-154 has minimal inotropic action, induces a significant "oxygen waste", and decreases vascular resistance in intact pigs. A potent phosphodiesterase inhibitory effect may explain this, which suggests further drug refinement.

3',5'-Cyclic-AMP Phosphodiesterases↗