Pressure-volume Area Research Articles

Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection

To determine whether adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest and improved cardioprotection. Cold crystalloid cardioplegia with adenosine, procaine and magnesium (A) was compared with standard cold crystalloid hyperkalemic cardioplegia (K). Sixteen pigs were randomized to receive either cold K (n=8) or A (n=8), where hyperkalemia was substituted with 1.2 mM adenosine. The cold (6 degrees C) cardioplegia was given intermittently and antegradely, with an aortic cross-clamp time of 1 h. Hemodynamic data was continuously measured and pressure-volume conductance catheters were used to determine global left ventricular systolic and diastolic function. Coronary flow and O2 content differences allowed determination of left ventricular energetics. Blood samples, and left ventricular microdialysis were used to measure parameters of ischemia. Measurements were done at 1 and 2 h after cross-clamp release. Mean arterial pressure was reduced with 55 mmHg (standard deviation, SD: 19) in the K group versus 30 mmHg (SD: 14) in the A group 2 h after cross-clamp release (p=0.030). Left ventricular contractility expressed as slope of the preload recruitable stroke work index (Mw) was reduced to 53% (SD: 14) in the K group versus 78% (SD: 23) in the A group 2h after cross-clamp release (p=0.046). Reduction of maximum of first derivate of pressure with respect to time (dP/dtmax) was 804 mmHg/s (SD: 189) in the K group versus 538 mmHg/s (SD: 184) in the A group (p=0.033). The slope of the myocardial oxygen consumption-pressure volume area was at 2 h reperfusion increased from 1.37 (SD: 0.64) to 2.86 (SD: 1.27) in the K group, whereas no shift was detected in the A group (p=0.019). Cardiac troponin T measured in the coronary sinus 1 h after cross-clamp release was 1.25 microg/l (SD: 0.64) in the K group versus 0.73 microg/l (SD: 0.31) in the A group (p=0.046). Adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest, improves post cardioplegic left ventricular systolic function and efficiency, and attenuates myocardial cell damage.

Altered left ventricular–arterial coupling precedes pump dysfunction in early heart failure

The objective of this study was to define alterations in ventricular-arterial (V-A) coupling early in the development of tachycardia-induced heart failure (HF). Although HF is characterized by impaired V-A coupling, the temporal relationship of these derangements to overt left ventricular (LV) dysfunction is unknown. Six anesthetized dogs instrumented with LV manometers and piezoelectric crystals were studied before and after 24 h of rapid ventricular pacing (RVP). V-A coupling was indexed by the ratio between the end-systolic pressure-volume relation slope (endsystolic elastance, E(ES)) and effective arterial elastance (E(A)), and mechanical efficiency by the ratio of stroke work (SW) to pressure-volume area (PVA). After RVP, there was no significant depression of LV function, but E(A) and total peripheral resistance (R(T)) were increased (P < 0.05), indicating increased arterial load. After RVP, E(ES)/E(A) and SW/PVA were maintained during unstressed conditions, but upon changes in load induced by phenylephrine, E(ES)/E(A) declined more precipitously with equivalent increases in R (T) (slope E(ES)/E(A)-R(T) relation -16.7 +/- 4.6 vs -5.8 +/- 4.0 ml/mmHg.min, P < 0.025). Furthermore, after RVP there was significant (P < 0.05) blunting of dobutamine-induced augmentation of E(ES), E(ES)/E(A), and SW/PVA. Thus, after RVP there was a distinct loss of V-A coupling reserve during afterload and catecholamine stress. V-A coupling defects occur early in the development of tachycardia-induced HF prior to significant pump dysfunction, and are manifested primarily during hemodynamic and inotropic stress.

Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts

The aim of this study was to examine how global cardiac gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) can influence left ventricular (LV) mechanical and energetic function, especially in terms of O(2) cost of LV contractility, in normal rats. Normal rats were randomized to receive an adenovirus carrying the SERCA2a (SERCA) or beta-galactosidase (beta-Gal) gene or saline by a catheter-based technique. LV mechanical and energetic function was measured in cross-circulated heart preparations 2-3 days after the infection. The end-systolic pressure-volume relation was shifted upward, end-systolic pressure at 0.1 ml of intraballoon water volume was higher, and equivalent maximal elastance, i.e., enhanced LV contractility, was higher in the SERCA group than in the normal, beta-Gal, and saline groups. Moreover, the LV relaxation rate was faster in the SERCA group. There was no significant difference in myocardial O(2) consumption per beat-systolic pressure-volume area relation among the groups. Finally, O(2) cost of LV contractility was decreased to subnormal levels in the SERCA group but remained unchanged in the beta-Gal and saline groups. This lowered O(2) cost of LV contractility in SERCA hearts indicates energy saving in Ca(2+) handling during excitation-contraction coupling. Thus overexpression of SERCA2a transformed the normal energy utilization to a more efficient state in Ca(2+) handling and superinduced the supranormal contraction/relaxation due to enhanced Ca(2+) handling.

Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

The aim of this study was to examine whether short- and long-term gene transfer of Ca 2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca 2+-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or β-galactosidase (Banding + βgal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. “Banding”, “Banding + βgal” and “Banding + saline” groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP 0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP 0.1) and slower LV relaxation rate, compared with “Normal” and “Sham”. However, “Banding + SERCA” and “Banding + Parv” showed high ESP 0.1, low EDP 0.1 and fast LV relaxation rate. In “Banding”, “Banding + βgal” and “Banding + saline”, slope of relation between cardiac oxygen consumption and systolic pressure–volume area, O 2 cost of total mechanical energy, was twice higher than normal value, whereas slope in “Baning + SERCA” and “Banding + Parv” was similar to normal value. Furthermore, O 2 cost of LV contractility in the 3 control banding groups was ∼ 3 times higher than normal value, whereas O 2 cost of contractility in “Banding + SERCA”, “Banding + AAV.SERCA” and “Banding + Parv” was as low as normal value. Thus, high O 2 costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO2) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-γ (PPARγ) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO2 was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO2, while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARγ-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice.

Inhibition of Endogenous Nitric Oxide Synthase Augments Contractile Response to Adenylyl Cyclase Stimulation Without Altering Mechanical Efficiency in Patients With Idiopathic Dilated Cardiomyopathy

Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure. The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency. These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.

The Acute Effect of Intra‐aortic Balloon Counterpulsation During Extracorporeal Life Support: An Experimental Study

Hemodynamically unstable patients supported by an extracorporeal life support (ECLS) circuit often receive additional support by intra-aortic balloon pump (IABP). However, it is not established whether support of the failing heart is improved by adjunctive IABP in both peripheral cannulation (PC) and central cannulation (CC) settings. Seven sheep were supported by an IABP and an ECLS system which were cannulated centrally as well as peripherally. In each cannulation configuration, hemodynamic and cardiac function indices were measured at baseline, ECLS, and ECLS plus IABP. The primary variables were mean coronary artery flow (Qcor), diastolic pressure time index (DPTI), left ventricular (LV) pressure-volume area (PVA), and tension time index (TTI). Additional IABP with ECLS support (CC/PC) decreased LV afterload (LV systolic peak pressure -4%, P<0.05/-8%, P<0.02), as well as TTI -2%/-10% and PVA -10%/-12% (P<0.03). Coronary perfusion was increased by additional IABP: CC, Qcor, +9%, and DPTI, +18% (P<0.02); PC, Qcor,+6%, and DPTI, +11% (P<0.05). IABP augmented the myocardial oxygen supply/demand ratios (CC/PC): Qcor/(PVA.heart rate) (+21%/+22%, P<0.02) and DPTI/TTI (+27%/+24%, P<0.03). In case of low arterial pressure (<50 mm Hg) and reduced ECLS flow, the overall hemodynamic profile improved only with central cannulation. We conclude that in both central and peripheral ECLS cannulation settings, adjunctive IABP improves the myocardial oxygen supply demand balance. In case of low cardiac output and insufficient extracorporeal flow with PC, adjunctive IABP may be contraindicated.

Sensorimotor Integration in S2, PV, and Parietal Rostroventral Areas of the Human Sylvian Fissure

We explored cortical fields on the upper bank of the Sylvian fissure using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to measure responses to two stimulus conditions: a tactile stimulus applied to the right hand and a tactile stimulus with an additional movement component. fMRI data revealed bilateral activation in S2/PV in response to tactile stimulation alone and source localization of MEG data identified a peak latency of 122 ms in a similar location. During the tactile and movement condition, fMRI revealed bilateral activation of S2/PV and an anterior field, while MEG data contained one source at a location identical to the tactile-only condition with a latency of 96 ms and a second rostral source with a longer latency (136 ms). Furthermore, Region-of-interest analysis of fMRI data identified increased bilateral activation in S2/PV and the rostral area in the tactile and movement condition compared with the tactile only condition. An area of cortex immediately rostral to S2/PV in monkeys has been called the parietal rostroventral area (PR). Based on location, latency, and conditions under which this field was active, we have termed the rostral area of human cortex PR as well. These findings indicate that humans, like non-human primates, have a cortical field rostral to PV that processes proprioceptive inputs, both S2/PV and PR play a role in somatomotor integration necessary for manual exploration and object discrimination, and there is a temporal hierarchy of processing with S2/PV active prior to PR.

Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer

The Otsuka–Long–Evans Tokushima Fatty rat represents a model for spontaneous non-insulin-dependent type II diabetes mellitus (DM), characterized by diastolic dysfunction and associated with abnormal calcium handling and decrease in sarcoplasmic reticulum Ca2+ -ATPase (SERCA2a) expression. The aim of this study was to examine whether SERCA2a gene transfer can restore the energetic deficiency and left ventricular (LV) function in this model. DM rats were randomized to receive adenovirus carrying either the SERCA2a gene (DM + Ad.SERCA2a) or the β-galactosidase gene (DM + Ad.βGal) or saline (DM + saline). LV mechanoenergetic function was measured in cross-circulated heart preparations 3 days after infection. In DM, end-systolic pressure at 0.1 ml intraballoon water (ESP0.1) was low and end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) was high (22 mm Hg), compared with non-DM (EDP0.1 12 mm Hg). In DM + Ad.SERCA2a, however, ESP0.1 was increased over 200 mm Hg and EDP0.1 was decreased to 7 mm Hg. LV relaxation rate was fast in DM + Ad.SERCA2a, but slow in the other DM groups. There was no difference in relation between cardiac oxygen consumption per beat and systolic pressure–volume area among all groups. Finally, the oxygen cost of LV contractility in DM was about three times as high as that of normal. In DM + Ad.SERCA2a, the oxygen cost decreased to control levels, but in DM + Ad.βGal/DM + saline it remained high. In DM failing hearts, the high oxygen cost indicates energy wasting, which contributes to the contractile dysfunction observed in diabetic cardiomyopathy. SERCA2a gene transfer transforms this inefficient energy utilization into a more efficient state and restores systolic and diastolic function to normal.

Increased Myocardial Oxygen Consumption Reduces Cardiac Efficiency in Diabetic Mice

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVo(2). Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.

Celsior Preserved Cardiac Mechanoenergetics Better Than Popular Solutions in Canine Hearts

Better protective effects of Celsior on cardiac function than the other conventional solutions have been reported in acute experiments and in clinical trials for at-risk patients. However, no study has yet precisely elucidated how these preservation solutions affect cardiac mechanoenergetics. Therefore, we evaluated the effects of St. Thomas' Hospital solution No. 2, University of Wisconsin solution, and Celsior on left ventricular contractility (Emax: end-systolic pressure-volume ratio) and oxygen consumption. We used 32 canine excised cross-circulated hearts. Twenty-three hearts served as donor hearts after hypothermic ischemia with one of the three solutions, and the remaining 9 served as controls. After arrest with each solution, the hearts were preserved for 4 hours at 4 degrees C. Then, we measured left ventricular pressure, volume, and oxygen consumption to obtain Emax and the relation between ventricular pressure-volume area (a measure of total mechanical energy) and oxygen consumption. We also evaluated the oxygen cost of Emax by changing Emax with calcium administration. Celsior did not significantly affect E(max) (6.3 +/- 2.4 in control versus 5.3 +/- 1.3 mm Hg.mL(-1).100 g with Celsior) nor the oxygen cost of Emax (1.2 +/- 0.6 versus 1.6 +/- 0.5 mL O2.mL.mm Hg(-1).beat(-1).100 g(-2), respectively). In contrast, St. Thomas' Hospital and University of Wisconsin solutions significantly decreased Emax (4.5 +/- 1.1 and 3.5 +/- 0.9 mm Hg.mL(-1).100 g, respectively) and increased the oxygen cost of Emax (2.5 +/- 0.8 and 2.4 +/- 0.9 mL O2.mL.mm Hg(-1).beat(-1).100 g(-2), respectively) compared with control and Celsior-preserved hearts. The slope and intercept of the oxygen consumption versus pressure-volume area relation showed no significant difference among the four groups. Celsior showed better protective effects on cardiac mechanoenergetics than St. Thomas' Hospital and University of Wisconsin solutions in the acute phase of heart transplantation.

Effects of Dopamine and Olprinone on Ventricular Energetics in Sevoflurane-Induced Acute Left Ventricular Depression in Dogs

The purpose of this study was to compare the effects of dopamine and a new phosphodiesterase (PDE)-3 inhibitor, olprinone, on hemodynamics and myocardial energetics in dogs with acute myocardial depression. Prospective, randomized, crossover study. University animal laboratory. Mongrel dogs. Eight open-chest, barbiturate-anesthetized dogs with instruments for measurement of left ventricular pressure and volume were exposed to 2 MAC (minimum alveolar concentration) of sevoflurane to induce acute myocardial depression. Each dog was randomly assigned for either infusion of dopamine (5 microg/kg/min) for 15 minutes or bolus of olprinone (10 microg/kg), followed by an infusion (0.3 microg/kg/min) for 30 minutes. Treatment was crossed over after a washout period of 90 minutes. For analysis of ventricular energetics, ventriculoarterial coupling was assessed using the ratio of arterial elastance to end-systolic pressure-volume relation and mechanical efficiency was calculated using the ratio of external work to pressure-volume area. Measurements were performed prior to sevoflurane administration, and before and after treatment. Two MAC of sevoflurane significantly impaired ventriculoarterial coupling and mechanical efficiency. Both olprinone and dopamine improved ventriculoarterial coupling and mechanical efficiency to similar degrees, but by different mechanisms. Olprinone improved ventricular energetics at a lower energy expenditure, probably because of olprinone's vasodilating effect, which augments energy transfer from the ventricle into the systemic circulation. Although both dopamine and olprinone improve sevoflurane-induced impairment of ventricular energetics, olprinone accomplishes this with lower ventricular energy expenditure.

In vivo assessment of coronary artery angioplasty and stent deployment from balloon pressure–volume data

This study assessed the clinical and practical value of angioplasty balloon pressure–volume data, obtained by a computer-controlled balloon inflation device, during standard percutaneous coronary intervention (PCI) procedures. Stent deployment was studied for 57 lesions in 34 patients. Angiographic predilation data were available in 9 patients. Vessel lumen improvement with pre-dilation was determined using the area difference under the pressure–volume curves of two consecutive inflations and compared to the angiographically determined lumen improvement. Stent opening pressure, the inflation volume needed to unfold the stent and the shape of the pressure–volume curve were assessed for differences between stent sizes (diameter, length) and manufacturer types. A Pearson correlation of 0.8 between the pressure–volume area difference and the angiographic lumen improvement was significant (p = 0.01), confirming that pressure–volume curves are useful in assessing lumen improvement after pre-dilation. There was a significant difference in stent opening pressure between stent types but not between different stent sizes (length, diameter). The inflation volume measured during the unfolding process of the stent correlated with the calculated stent lumen when deployed (Pearson correlation: 0.65, p = 0.001). The shape of the pressure–volume curve during stent deployment illustrated differences between different stent sizes (length, diameter) during inflation. Pressure–volume curves obtained from an automatic balloon inflation device have shown their usefulness in providing additional feedback about lumen improvement and the mechanical characteristics and quality of stent deployment.

The Impact of Rotary Blood Pump in Conjunction with Mechanical Ventilation on Ventricular Energetic Parameters

Aim of this work is to study the impact of left ventricular rotary blood pump assistance, on energetic variables, when mechanical ventilation (MV) of the lungs is applied. Computer simulation was used to perform this study. Lumped parameter models reproduce the circulatory system. Variable elastance models reproduce the Starling's law of the heart for each ventricle. After the reproduction of ischemic heart disease left ventricular assistance was applied using a model of rotary blood pump. The pump speed was changed in steps and was assumed to be constant during each step. The influence of mechanical ventilation was introduced by different values of positive mean thoracic pressure. The increase of the rotational speed has a significant influence on some ventricular energetic variables. In fact it decreased left ventricular external work, left and right ventricular pressure-volume area and the left ventricular efficiency. Finally, it increased the right ventricular efficiency but had no influence on the right ventricular external work. The increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of external work, pressure-volume area (right ventricular pressure-volume area dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while left ventricular efficiency remained almost stable. Numerical simulation is a very suitable tool to predict changes of not easily measurable parameters such as energetic ventricular variables when mechanical assistance of heart and/or lungs is applied independently or simultaneously.

High Mechanical Efficiency of Left Ventricular Arrhythmic Contractions during Atrial Fibrillation

We analyzed the frequency distribution of the left ventricular (LV) mechanical efficiency of individual arrhythmic beats during electrically induced atrial fibrillation (AF) in normal canine hearts. This efficiency is the fraction of the external mechanical work (EW) in the total mechanical energy measured by the systolic pressure-volume area (PVA). The mean, median, and mode of this efficiency (EW/PVA) were as high as 78%, 80%, and 81%, respectively, on average in six hearts. These high efficiencies were comparable to that of the regular beats in these hearts. The frequency distribution of the EW/PVA during AF tended to skew to the higher side in all the hearts. Since the EW/PVA is directly related to both the ventriculo-arterial (or afterload) coupling ratio (E(a)/E(max); E(a) = effective arterial elastance, E(max) = end-systolic ventricular elastance) and the ejection fraction on a per-beat basis, we also analyzed their frequency distributions. We found them to skew enough to account for the rightward skewed frequency distribution of the EW/PVA during AF with the unexpectedly high mean EW/PVA. These results indicate that the LV arrhythmia during AF per se does not directly suppress the mean level of LV mechanical efficiency in normal canine hearts.

Detrimental effects after dobutamine infusion on rat left ventricular function: mechanical work and energetics

We have previously reported that continuous infusion of dobutamine into the coronary artery induces positive inotropic effects but induces no detrimental effects in cross-circulated, excised normal rat hearts and even in Ca2+ overload-induced contractile failing rat hearts. However, we hypothesized that some detrimental effects on left ventricular (LV) function are induced after continuous dobutamine infusion and the following clearance of blood dobutamine, as is the case after beta-adrenergic receptor stimulation. To test this hypothesis, we investigated LV mechanical work and energetics in the same type of preparations that underwent continuous dobutamine infusion and clearance of blood dobutamine. We found that both mean end-systolic pressure and systolic pressure-volume area (PVA; a measure of total mechanical energy per beat) at midrange LV volume were significantly (P < 0.01) decreased. The mean myocardial oxygen consumption per beat intercept, which is composed of for the total Ca2+ handling in excitation-contraction coupling and basal metabolism, of the and PVA linear relation was also significantly (P < 0.05) decreased (n=8). The mean slope of the linear relation was unchanged in such hearts. Post-dobutamine basal metabolism was unchanged (n = 5 of the 8 hearts). The moderate proteolysis of a cytoskeleton protein, alpha-fodrin was identified (n = 7 of the 8 hearts with the decreased intercept), after clearance of blood dobutamine. In agreement with our hypothesis, the detrimental effect of the post-beta-adrenergic receptor stimulation was induced by a moderate concentration of dobutamine; we found systolic dysfunction due to the impairment of Ca2+ handling in excitation-contraction coupling in the rat LV and proteolysis of a cytoskeleton protein, alpha-fodrin.

Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts

In the present study, we tested the reliability of measurements of pressure-volume area (PVA) and oxygen consumption (MVo(2)) in ex vivo mouse hearts, combining the use of a miniaturized conductance catheter and a fiber-optic oxygen sensor. Second, we tested whether we could reproduce the influence of increased myocardial fatty acid (FA) metabolism on cardiac efficiency in the isolated working mouse heart model, which has already been documented in large animal models. The hearts were perfused with crystalloid buffer containing 11 mM glucose and two different concentrations of FA bound to 3% BSA. The initial concentration was 0.3 +/- 0.1 mM, which was subsequently raised to 0.9 +/- 0.1 mM. End-systolic and end-diastolic pressure-volume relationships were assessed by temporarily occluding the preload line. Different steady-state PVA-MVo(2) relationships were obtained by changing the loading conditions (pre- and afterload) of the heart. There were no apparent changes in baseline cardiac performance or contractile efficiency (slope of the PVA-MVo(2) regression line) in response to the elevation of the perfusate FA concentration. However, all hearts (n = 8) showed an increase in the y-intercept of the PVA-MVo(2) regression line after elevation of the palmitate concentration, indicating an FA-induced increase in the unloaded MVo(2). Therefore, in the present model, unloaded MVo(2) is not independent of metabolic substrate. This is, to our knowledge, the first report of a PVA-MVo(2) relationship in ex vivo perfused murine hearts, using a pressure-volume catheter. The methodology can be an important tool for phenotypic assessment of the relationship among metabolism, contractile performance, and cardiac efficiency in various mouse models.

Positive inotropic effect of nicorandil in adult rats in situ

Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system. We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure-volume relations (ESPVRs), LV end-systolic pressure (ESP(mLVV)), and systolic pressure-volume area (PVA(mLVV)) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea). Nicorandil (10 and 20 microg.kg(-1).min(-1)) (blood concentration: 0.53 +/- 0.14 and 1.48 +/- 0.21 microg/ml) largely shifted ESPVR upward and thus significantly increased ESP(0.06), PVA(0.06), stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 microg.kg(-1) . min(-1)), significantly decreased Ea but did not change ESP(0.06), PVA(0.06), and EDV. Furthermore, either a nonselective K(ATP) channel blocker, glybenclamide, or a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions. These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).

The effects of cardiac cooling under surface-induced hypothermia on the cardiac function in the in situ heart

It has been reported that in the excised cross-circulated dog heart model, cardiac cooling increases Emax (contractility index) and the external work (EW) of the left ventricle without affecting the systolic pressure volume area (PVA)-independent myocardial oxygen consumption (VO2). However, it remains unclear whether this cooling inotropism and oxygen-saving effect can also be demonstrated in an in situ heart. In the present study, we investigated the effect of cardiac cooling under surface-induced hypothermia in the in situ heart to assess the practical application of this method. Adult mongrel dogs were examined under surface-induced hypothermia with or without vasodilator. Using conductance catheter, pressure-volume relationship were obtained and mechanoenergetical parameters were measured. Optimal temperature for cardiac cooling was also examined. Simple hypothermia increased Emax compared with normothermia without affecting PVA-independent VO2, but EW did not increase. However, with concurrent vasodilator administration, cardiac cooling increased not only Emax but also EW without affecting PVA-independent VO2 compared with normothermia. However, at temperature below 32 degrees C, Tau increased significantly and diastolic dysfunction was noted. Cardiac cooling with concurrent vasodilator administration in the in situ heart has inotropic and oxygen-saving effects and optimal temperature for cardiac cooling is thought to be 34 degrees C.

Predictability of O2 Consumption from Contractility and Mechanical Energy of Absolute Arrhythmic Beats in Canine Heart

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.