Constant Heart Rate Research Articles

FLIGHTLESSNESS AND THE ENERGETIC COST OF WING MOLT IN A LARGE SEA DUCK

Although the replacement of feathers apparently represents the major event of somatic production in the annual cycle of wild birds, knowledge about the energetics of molt has always been hampered by logistical and technical difficulties, which are exacerbated by the fact that birds are able to compensate behaviorally to buffer any variation in energy demand. During wing molt, sea ducks (Mergini) and other diving birds lose all of their wing feathers at once, leading to a period of temporary flightlessness of variable duration, a condition that considerably restricts their movements and increases the probability of predation. In the present study, we present the first results aimed at quantifying the duration of flightlessness, energy expenditure, and foraging effort during molt of a wing-propelled diving bird, the Common Eider (Somateria mollissima). Data loggers were implanted in the body cavity of 13 females to record heart rate and hydrostatic pressure (depth) every two seconds for a period of 220 days. Flight frequency and duration were assessed from elevated and constant heart rate, and the absence of flight was used to quantify the duration of flightlessness, which lasted, on average, 36 +/- 8 days (mean +/- SD). Using a period of four weeks before and four weeks after the flightless period, we found that dive depth (ranging from 1 to 2 m, on average) and daily diving time did not vary during the course of the study. Daily metabolic rate increased by 9%, and resting metabolic rate by 12% from the pre-molt period to the flightless period and remained high during the post-molt period. This study indicates that the energetic costs of replacing flight remiges in female eiders are substantial, although this is not associated with any change in foraging effort, which suggests that female Common Eiders lose mass during wing molt. Finally, estimates of energy savings associated with the total absence of flights during wing molt represent 6% of daily metabolic rate or 14% of resting metabolic rate. This finding contrasts with the classical view that little or no benefit is associated with a flightless condition. We suggest that such energy savings may have favored the evolution of temporary flightlessness in diving birds.

Prolactin Induces Regional Vasoconstriction through the β2-Adrenergic and Nitric Oxide Mechanisms

Prolactin has been associated with many effects and has been implicated in the pathogenesis of pregnancy-related hypertensive disorders, although little is known about its vascular effects. The present study was designed to determine the primary effect of prolactin on regional vascular beds and the mechanisms involved. In 37 anesthetized pigs, the infusion of 0.17 mug/kg min of prolactin at constant heart rate and arterial pressure decreased coronary, mesenteric, renal, and iliac blood flow. This response was graded in further five pigs by increasing the infused dose of the hormone between 0.017 and 1 mug/kg min. In 22 of the 37 pigs, blockade of cholinergic receptors (five pigs) and of alpha-adrenoceptors (five pigs) did not affect the prolactin-induced vascular response, which was abolished by blockade of beta(2)-adrenoceptors (five pigs) and by blockade of vascular nitric oxide (NO) synthase (seven pigs). In 15 of the 37 pigs the increases in measured blood flows caused by iv infusion of isoproterenol (five pigs) and by intraarterial administration of acetylcholine (five pigs) and of sodium nitroprusside (five pigs) were significantly reduced by infusion of prolactin. Moreover, the treatment of porcine aortic endothelial cells by prolactin caused a reduction of NO production and of the phosphorylation of ERK, Akt, and p38, which was prevented by the concomitant treatment by the beta(2)-adrenergic agonist albuterol. The present study showed that iv infusion of prolactin primarily caused coronary, mesenteric, renal, and iliac vasoconstriction. These effects were brought about by the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the NO intracellular pathway.

Intracoronary Ghrelin Infusion Decreases Coronary Blood Flow in Anesthetized Pigs

The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.

ANG II-induced hypertension and the role of the area postrema during normal and increased dietary salt

It has been shown that the area postrema (AP) plays a role in the development of certain types of chronic angiotensin II (ANG II)-induced hypertension in the rat but is not of great importance in the salt sensitivity of arterial pressure. It has recently been proposed, however, that elevated sodium levels may exacerbate the hypertensive effects of ANG II, which by itself dramatically affects salt sensitivity, by acting at sodium-sensing neurons in certain circumventricular organs of the brain. Thus the interactions of ANG II, sodium, and the central nervous system remain to be fully understood. The purpose of this study was to examine the role of the AP in ANG II-induced hypertension during periods of normal and elevated dietary salt. We hypothesized that an intact AP was necessary for the full development of hypertension under chronic ANG II infusion and that its role would be pronounced during periods of increased dietary sodium. To test this, male Sprague-Dawley rats underwent ablation of the area postrema (APx, n = 6) or sham operation (sham, n = 6). After 3 wk of recovery, rats were instrumented with radiotelemetry transducers for constant blood pressure and heart rate monitoring and venous catheters for vehicle infusion. After a 3-day control period of 0.9% saline infusion (7 ml/day) and 0.4% dietary sodium, a 10-day period of ANG II infusion (10 ng.kg(-1).min(-1)) was begun, immediately followed by a second 10-day period during which rats were fed a 4.0% sodium diet. By day 6 of ANG II infusion, mean arterial pressure (MAP) in APx rats had increased to 139 +/- 4 mmHg, whereas MAP in sham rats had increased to 126 +/- 3 mmHg. This difference was found to be significant and continued through day 1 of the high-salt period, after which MAP of the two groups had risen to similar levels. On day 9 of high salt, MAP was again observed to be significantly higher (162 +/- 1 mmHg) in APx rats when compared with sham rats (147 +/- 4 mmHg.) These results do not support the hypothesis that the AP is necessary for the full development of ANG II-induced hypertension at normal or elevated levels of dietary sodium.

The Reliability and Validity of Running Speed Variance by Heart Rate Control (RSVHRC) on Treadmill

Nowadays, the exercise equipment manufacturers have added heart-rate-monitor controlled programs to their equipment popularly. To compare common performance in running studies, like maximum oxygen uptake or critical velocity, which always let subjects to exhaustion however using the function of heart rate control on treadmill could be a new material to assess aerobic fitness under sub-maximal running intensity. PURPOSE: To assess the reliability and validity in measuring aerobic fitness of the protocol of running speed variance by heart rate control (RSVHRC, running at 80% of age-predicted maximum heart rate) on treadmill. METHODS: Subjects were 44 volunteer Taiwan college students (28 males and 16 females, age: 20.82+2.75 yrs, height: 168.93+6.75 cm, weight: 62.90+9.87 kg) who were asked to run twice by the RSVHRC protocol on treadmill one day apart at least. The RSVHRC protocol asked subjects to warm up 3 minutes at 6 km/h. When the end of warming up, subjects' heart rate were over 120 beats/min, the velocity start at 9 km/hr otherwise at 10 km/hr then turned up or down 0.5 km/hr every 30 seconds to keep constant heart rate at 80% of age-predicted maximum heart rate. Following this, partial participants (21 males and 5 females) were asked to undergo a graded treadmill test using the modified Bruce testing protocol, in order to acquire the measure of VO2max. Using the linear regression of time and running distance to determine RSVHRC and measure the reliability and validity by Pearson Product Moment correlation coefficient. RESULTS: Treadmill RSVHRC (2.50+0.59 m/s, male: 2.73+0.53 m/s, female: 2.08+0.44 m/s) was associated with VO2max (49.80+;7.06 ml/kg/min, male: 51.38+5.58 ml/kg/min, female 40.78+5.50 ml/kg/min) at rvalues at .73, .79 and .75, respectively (p < 0.05). The test-retest reliability of RSVHRC (2.58+0.62 m/s, male: 2.84+0.58 m/s, female: 2.13+0.39 m/s) was significant correlation to the first time (r = .95, .93 and .94, respectively, p < 0.05) and no significant difference between two test (p > 0.05). CONCLUSIONS: Running at 80% of age-predicted maximum on a treadmill, using RSVHRC, is a reliable and valid protocol for measuring aerobic fitness and this measure is highly recommended for its practical usage on the treadmill for its easy execution and simple testing procedures.

Effect of Exercise at Constant Heart Rate on Maximal Oxygen Uptake During Heat Stress

PURPOSE: To determine whether elimination of cardiovascular drift (CV drift) during prolonged exercise by holding heart rate (HR) constant reduces or eliminates the decrease in maximal oxygen uptake (VO2max) associated with CV drift. METHODS: After a control VO2max test, seven active males completed three sessions in which they cycled at 60% VO2max in 35 degrees C for 15 min, 45 min while HR was allowed to rise over time (HRvar), and 45 min while HR was held constant (at the 8-min value) by computer-adjusted work rate (HRcon). Each bout of submaximal exercise was followed immediately by a graded exercise test (GXT) to measure VO2max. The 15- and 45-min trials were intended to measure VO2max during the same time interval in which CV drift occurred. RESULTS: Between 15 and 45 min, a 13% increase inHR (149±12 vs. 169±14 bpm, P=0.001) and 10% decrease in SV (107±11 vs. 96±7 mL/beat, P=0.004) was accompanied by a 15% decrease in VO2max (4.1±0.4 vs. 3.5±0.5 L/min, P<0.05) in HRvar, while HR remained constant in HRcon (P>0.05), which corresponded to a smaller decrease in VO2max (7.5%, P=0.003). Power output had to be lowered ∼37% from 15 to 45 min in HRcon in order to keep HR constant. Percent VO2max increased from 59±6% at 15 min to 72±8% at 45 min in HRvar, whereas it decreased in HRcon at 45 min to 50±5%. CONCLUSION: Eliminating CV drift by holding HR constant only partially eliminated the reduction in VO2max after prolonged exercise in the heat. Relative metabolic intensity must be lowered by about 10 percentage points (from 60% to 50% VO2max) in order for HR to be held constant under hot conditions like those imposed in this study.

The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs

Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of beta2-adrenergic receptors. Since nitric oxide is known to modulate or mediate beta2-adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of beta2-adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release.

Experimental Conditions Are Important Determinants of Cardiac Inotropic Effects of Propofol

The rationale for this study is that the depressant effect of propofol on cardiac function in vitro is highly variable but may be explained by differences in the temperature and stimulation frequency used for the study. Both temperature and stimulation frequency are known to modulate cellular mechanisms that regulate intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in cardiac muscle. The authors hypothesized that temperature and stimulation frequency play a major role in determining propofol-induced alterations in [Ca2+]i and contraction in individual, electrically stimulated cardiomyocytes and the function of isolated perfused hearts. Freshly isolated myocytes were obtained from adult rat hearts, loaded with fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte shortening were simultaneously measured in individual cells at 28 degrees or 37 degrees C at various stimulation frequencies (0.3, 0.5, 1, 2, and 3 Hz) with and without propofol. Langendorff perfused hearts paced at 180 or 330 beats/min were used to assess the effects of propofol on overall cardiac function. At 28 degrees C (hypothermic) and, to a lesser extent, at 37 degrees C (normothermic), increasing stimulation frequency increased peak shortening and [Ca2+]i. Times to peak shortening and rate of relengthening were more prolonged at 28 degrees C compared with 37 degrees C at low stimulation frequencies (0.3 Hz), whereas the same conditions for [Ca2+]i were not altered by temperature. At 0.3 Hz and 28 degrees C, propofol caused a dose-dependent decrease in peak shortening and peak [Ca2+]i. These changes were greater at 28 degrees C compared with 37 degrees C and involved activation of protein kinase C. At a frequency of 2 Hz, there was a rightward shift in the dose-response relation for propofol on [Ca2+]i and shortening at both 37 degrees and 28 degrees C compared with that observed at 0.3 Hz. In Langendorff perfused hearts paced at 330 beats/min, clinically relevant concentrations of propofol decreased left ventricular developed pressure, with the effect being less at 28 degrees C compared with 37 degrees C. In contrast, only a supraclinical concentration of propofol decreased left ventricular developed pressure at 28 degrees C at either stimulation frequency. These results demonstrate that temperature and stimulation frequency alter the inhibitory effect of propofol on cardiomyocyte [Ca2+]i and contraction. In isolated cardiomyocytes, the inhibitory effects of propofol are more pronounced during hypothermia and at higher stimulation frequencies and involve activation of protein kinase C. In Langendorff perfused hearts at constant heart rate, the inhibitory effects of propofol at clinically relevant concentrations are more pronounced during normothermic conditions.

Maximal Constant Heart Rate - A Heart Rate Based Method to Estimate Maximal Lactate Steady State in Running

The aim of the present study was to investigate the accuracy of the maximal constant heart rate method for predicting anaerobic threshold (AnT) in running. This method only requires a common heart rate (HR) monitor and is based on the identification of the maximal constant HR maintainable for 30 min (HRMC). HRMC, 4-mmol threshold, and maximal lactate steady state (MLSS) were determined in 31 probands. 17 probands underwent an additional MLSS retest within 2 weeks. The correlation between HR at MLSS and at MLSS retest was very close (r = 0.807; SEE = 5.25 beats x min(-1); p < 0.001). So were the correlations between HR at 4-mmol threshold and MLSS (r = 0.844; SEE = 6.43 beats x min(-1); p < 0.001) and between HRMC and HR at MLSS (r = 0.820; SEE = 6.73 beats x min(-1); p < 0.001). Mean velocities at maximum constant HR trials and MLSS (r = 0.895; SEE = 0.185 m x s(-1); p < 0.001) as well as 4-mmol threshold and MLSS (r = 0.899; SEE = 0.186 m x s(-1); p < 0.001) were highly correlated. In conclusion, data presented in this study confirm that the determination of HRMC is a manageable method giving a highly accurate estimation of both HR and velocity at MLSS in running.

Immediate effects of atrial contribution loss in sequentially paced patients demonstrated by non-invasive hemodynamic monitoring using the Finometer device.

was to find out which of the output parameters of a noninvasive finger arterial pressure evaluation device (Finometer®) is most sensitive to abrupt changes in systolic output of the left ventricle induced by loss of atrial contribution. A total of 15 hemodynamically stable patients aged 67±15 years were enrolled. All patients had dual chamber pacemakers enabling alternation between an atrioventricular delay (AVD) 170ms (period A) to an AVD 50ms (period B), while maintaining a constant heart rate and constant RR intervals. Beat-to-beat changes in systolic (sBP), diastolic (dBP) and mean (MP) arterial pressure and cardiac output (CO – calculated by the device from the shape of the individual pressure waves) were analyzed in a period of seven minutes in each setting. After the switchover, an average drop in CO (22%), sBP (15%), dBP (7%) and MP were recorded (period B). At the end of the seven-minute period (period C) all parameters returned to initial values apart from CO (lower by 9.4%, P &#60; 0.001). The abrupt fall in atrial contribution causes a drop in arterial pressure and CO. While the CO remains decreased, arterial pressure returns to the control level within 7 minutes. The Finometer device enables very sensitive analysis of hemodynamic changes induced by manipulation of the systolic output of the left ventricle.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node—ablated, His bundle-paced dog

Introduction: Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node—ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Methods: Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. Results: E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E max model with an effect site. Maximum RT change ( E max), free drug concentration at half of the maximum effect (EC 50), and free drug concentration associated with a 10 ms RT prolongation (EC 10 ms) were estimated. A linear correlation between EC 10 ms and HERG IC 50 values was identified. Discussion: The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I Kr inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Cardiovascular development in embryos of the American alligator Alligator mississippiensis: effects of chronic and acute hypoxia

Chronic hypoxic incubation is a common tool used to address the plasticity of morphological and physiological characteristics during vertebrate development. In this study chronic hypoxic incubation of embryonic American alligators resulted in both morphological (mass) and physiological changes. During normoxic incubation embryonic mass, liver mass and heart mass increased throughout the period of study, while yolk mass fell. Chronic hypoxia (10%O2) resulted in a reduced embryonic mass at 80% and 90% of incubation. This reduction in embryonic mass was accompanied by a relative enlargement of the heart at 80% and 90% of incubation, while relative embryonic liver mass was similar to the normoxic group. Normoxic incubated alligators maintained a constant heart rate during the period of study, while mean arterial pressure rose continuously. Both levels of hypoxic incubation (15% and 10%O2) resulted in a lower mean arterial pressure at 90% of incubation, while heart rate was lower in the 10%O2 group only. Acute (5 min) exposure to 10%O2 in the normoxic group resulted in a biphasic response, with a normotensive bradycardia occurring during the period of exposure and a hypertensive tachycardic response occurring during recovery. The embryos incubated under hypoxia also showed a blunted response to acute hypoxic stress. In conclusion, the main responses elicited by chronic hypoxic incubation, namely, cardiac enlargement, blunted hypoxic response and systemic vasodilation, may provide chronically hypoxic embryos with a new physiological repertoire for responding to hypoxia.

The Relationship between Exercise Capacity and the New Evaluation Method for Exercise Work by Controlling Pedaling Torque to a Constant Heart Rate Level during Exercise in Healthy Young Men and Women

The Relationship between Exercise Capacity and the New Evaluation Method for Exercise Work by Controlling Pedaling Torque to a Constant Heart Rate Level during Exercise in Healthy Young Men and Women

Ventilation‐synchronous magnetic resonance microscopy of pulmonary structure and ventilation in mice

Increasing use of transgenic animal models for pulmonary disease has raised the need for methods to assess pulmonary structure and function in a physiologically stable mouse. We report here an integrated protocol using magnetic resonance microscopy with gadolinium (Gd)-labeled starburst dendrimer (G6-1B4M-Gd, MW = 192 +/- 1 kDa, R(h) = 5.50 +/- 0.04 nm) and hyperpolarized (3)helium ((3)He) gas to acquire images that demonstrate pulmonary vasculature and ventilated airways in live mice (n = 9). Registered three-dimensional images of (1)H and (3)He were acquired during breath-hold at 2.0 T using radial acquisition (total acquisition time of 38 and 25 min, respectively). The macromolecular Gd-labeled dendrimer (a half-life of approximately 80 min) increased the signal-to-noise by 81 +/- 30% in the left ventricle, 43 +/- 22% in the lung periphery, and -4 +/- 5% in the chest wall, thus increasing the contrast of these structures relative to the less vascular surrounding tissues. A constant-flow ventilator was developed for the mouse to deliver varied gas mixtures of O(2) and N(2) (or (3)He) during imaging. To avoid hypoxemia, instrumental dead space was minimized and corrections were made to tidal volume lost due to gas compression. The stability of the physiologic support was assessed by the lack of spontaneous breathing and maintenance of a constant heart rate. We were able to stabilize the mouse for >8 hr using ventilation of 105 breath/min and approximately 0.2 mL/breath. The feasibility of acquiring both pulmonary vasculature and ventilated airways was demonstrated in the mouse lung with in-plane spatial resolution of 70 x 70 microm(2) and slice thickness of 800 microm.

Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol.

Several clinical trials have demonstrated that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) are equally effective in the treatment of chronic heart failure. However, this has not been confirmed for acute cardiac dysfunction. We examined whether ACEI or ARB prevents isoproterenol-induced acute left ventricular (LV) dysfunction in dogs. LV dysfunction induced by a large dose of isoproterenol (1 microg.kg(-1).min(-1), 3-h infusion) was compared in dogs treated with ACEI (temocaprilat) or ARB (olmesartan). Atrial pacing induced a constant heart rate and use of adjustable aortic banding provided a nearly constant afterload. LV systolic function (LV dP/dt, fractional shortening, and ejection fraction) and diastolic function (tau and LV end-diastolic pressure) were significantly deteriorated after isoproterenol infusion. The LV dysfunction was almost totally prevented by ARB but was only partially prevented by ACEI. The partial effect of ACEI was complemented by cotreatment with HOE-140, a bradykinin B2 receptor antagonist. At baseline, the response to low doses of isoproterenol was significantly attenuated by ACEI but not by ARB, and the ACEI-induced attenuation was totally abolished by cotreatment with HOE-140. The response to isoproterenol was significantly attenuated after 3 h of excess isoproterenol loading, and it was almost completely preserved by ARB but not by ACEI. In conclusion, acute LV dysfunction and beta-adrenergic desensitization induced by excess isoproterenol administration were almost totally prevented by ARB but only partially prevented by ACEI. These differences were attributable at least in part to bradykinin pathways activated by ACEI administration in acute LV dysfunction.

Impaired muscle metaboreflex-induced increases in ventricular function in heart failure.

We investigated to what extent heart failure alters the ability of the muscle metaboreflex to improve ventricular function. Dogs were chronically instrumented to monitor mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), stroke volume (SV), and central venous pressure (CVP) at rest and during mild treadmill exercise (3.2 km/h) before and during reductions in hindlimb blood flow imposed to activate the muscle metaboreflex. These control experiments were repeated at constant heart rate (ventricular pacing 225 beats/min) and at constant heart rate coupled with a beta-adrenergic blockade (atenolol, 2 mg/kg iv) in normal animals and in the same animals after the induction of heart failure (HF, induced via rapid ventricular pacing). In control experiments in normal animals, metaboreflex activation caused tachycardia with no change in SV, resulting in large increases in CO and MAP. At constant HR, large increases in CO still occurred via significant increases in SV. Inasmuch as CVP did not change in this setting and that beta-adrenergic blockade abolished the reflex increase in SV at constant HR, this increase in SV likely reflects increased ventricular contractility. In contrast, after the induction of HF, much smaller increases in CO occurred with metaboreflex activation because, although increases in HR still occurred, SV decreased thereby limiting any increase in CO. At constant HR, no increase in CO occurred with metaboreflex activation even though CVP increased significantly. After beta-adrenergic blockade, CO and SV decreased with metaboreflex activation. We conclude that in HF, the ability of the muscle metaboreflex to increase ventricular function via both increases in contractility as well as increases in filling pressure are markedly impaired.

The effects of insulin on mesenteric blood flow in anaesthetized pigs.

Infusion of insulin in anaesthetized pigs has been shown to cause an increase in renal blood flow and a decrease in coronary blood flow, which were the net result of a vasoconstriction involving sympathetic alpha-adrenoceptor-mediated mechanisms and of a local vasodilatation involving the endothelial release of nitric oxide. In the present study, the effect of insulin on superior mesenteric blood flow was examined in pentobarbitone-anaesthetized pigs at constant heart rate, aortic blood pressure, left ventricular contractility and blood levels of glucose and potassium. In 10 pigs, infusion of 0.004 IU kg(-1) min(-1) of insulin increased mesenteric flow. In five of these pigs, intravenous phentolamine enhanced the increase in mesenteric flow elicited by insulin, a response which was abolished by the subsequent injection of N(omega)-nitro-L-arginine methyl ester (L-NAME) into the mesenteric artery. In the remaining five pigs, infusion of insulin after intramesenteric injection of L-NAME caused a decrease in mesenteric flow. This response was abolished by the subsequent intravenous administration of phentolamine. The present study showed that infusion of insulin in anaesthetized pigs primarily caused a mesenteric vasodilatation, which was the net result of two opposite effects, namely a predominant vasodilatation mediated by the endothelial release of nitric oxide and a sympathetic vasoconstrictor mechanism mediated by alpha-adrenoceptors.

Flexible Textile Heartvalve Prosthesis: An In Vitro Evaluation

The hydrodynamic performances of fabric heartvalve protheses were measured and compared with other commercially available types of heartvalve prostheses. A prosthesis was manufactured by forming fabric to a geometry close to that of the native valve. In vitro performances of the prototype were evaluated using a pulse duplicator simulating the left side of the human circulatory system, with a 70 ml cardiac output at a constant heart rate of 70 beats/min under a mean diastolic pressure of 100 mmHg. Woven fabrics of different weaves, yarn structures (multifilaments and microfibres), saturation indexes, and rigidity were tested in terms of static and dynamic regurgitation, pressure drops across the valve, and dynamic behaviour. The results were found to be close to those expected for such a device and, in some respects (pressure drop), even better than those obtained with other prostheses in current use. The yarn structure and fabric saturation index seem to be important parameters in the development of a textile prosthesis. Thus, the tests showed that a plainweave structure with microfilament yarns and a reduced saturation index appears to be the fabric best suited for the valve application.

A fast and simple echocardiographic method of determination of the optimal atrioventricular delay in patients after biventricular stimulation.

The optimization of atrioventricular (AV) delay is known to significantly contribute to maximum cardiac performance. The aim of this study was to validate a new, fast, and simple echocardiographic method of identifying the AV delay that provides the maximum cardiac output (CO). Right heart catheterization and Doppler echocardiography of transmitral filling were performed simultaneously in 18 patients with heart failure and at least minimum functional mitral regurgitation treated with atrial synchronized biventricular pacing. CO derived from catheterization and Doppler filling parameters were measured at the predicted optimal AV delay (oAVD), the short AV delay (oAVD - 50 ms), and the long AV delay (oAVD + 28 ms on average/range, +10 ms to +50 ms) during a constant heart rate. The AV delay was regarded as optimal if the end of atrial contraction (represented by the end of A wave of transmitral filling) coincided with the beginning of ventricular contraction (heralded by the onset of the systolic component of mitral regurgitation). Prediction of the optimal AV delay included the following steps: (1) The maximum AV delay at which full ventricular capture is still preserved was found under electrocardiographic control. (2) This value, decreased by 5 to 10 ms, was designated as "the testing long AV delay," and the time interval from the end of the A wave to the onset of the systolic component of mitral regurgitation (time t1) was measured at this setting. (3) oAVD was simply calculated as "the testing long AV delay"- time t1. The CO measured at the oAVD (4.5 +/- 0.7 1. min-1) significantly exceeded those at the short AV delay (4.3 +/- 0.7 1. min-1, P < 0.01) and the long AV delay (4.4 +/- 0.8 1. min-1, P < 0.01), respectively. The method correctly determined the maximum CO in 78% of the patients. In conclusion, Doppler echocardiography enables very rapid and accurate optimization of AV synchrony in patients after the implantation of a biventricular pacemaker.

In vivo validation of cardiac spiral computed tomography using retrospective gating

Background Cardiac functional assessment represents the basis for diagnostics and cardiac operation planning. Spiral computed tomography (CT) combines the advantages of three-dimensional imaging and high temporal resolution when using gating techniques. However, in vivo validation data of this novel imaging technology are lacking. The purpose of this study was to validate in vivo the new imaging method using retrospective gating and to evaluate the clinical usefulness of the achieved temporal resolution. Methods In domestic pigs (n = 10, weight 35 to 40 kg) a flowmeter was placed surgically on the ascending aorta. Flow velocity integrated over systole served as the gold standard for left ventricular (LV) stroke volume (LVSV-FM). CT signal, projection data, pacemaker signal, and flow velocity were recorded simultaneously at constant heart rate (pacemaker, 90 beats per minute). End-systolic and end-diastolic frames were calculated by retrospective gating. LV volumes were traced, the difference representing CT stroke volume (LVSV-CT). Image data were three-dimensionally reconstructed using ray-tracing. Results Temporal resolution was 170 ms. Correlation of stroke volumes was high ( r = 0.94, mean difference 1.75 mL). Intraobserver (0.49 mL for LVEDV, 0.31 for LVESV) and interobserver variability ( p = 0.21 and p = 0.06, respectively) were low. Postprocessing resulted in four-dimensional beating-heart models useful for operation planning. Conclusions Spiral CT using retrospective gating was validated in vivo. Clinically acceptable temporal resolution and accuracy in determining cardiac stroke volumes were found. As a true volumetric imaging modality the method may now play an important role in computer-assisted diagnostics and surgery.