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Biomedical subjects

P Steendijk

Publications and source records attributed to P Steendijk.

At least 37 records · Page 2Linked to original sources

Improved contractile performance of right ventricle in response to increased RV afterload in newborn lamb.

Pulmonary hypertension results in an increased afterload for the right ventricle (RV). To determine the effects of this increased afterload on RV contractile performance, we examined RV performance before and during 4 h of partial balloon occlusion of the pulmonary artery and again after releasing the occlusion in nine newborn lambs. RV contractile performance was quantified by indexes derived from systolic RV pressure-volume relations obtained by a combined pressure-conductance catheter during inflow reduction. An almost twofold increase of end-systolic RV pressure (from 22 to 38 mmHg) was maintained during 4 h. Cardiac output (CO) (0.74 +/- 0.08 l/min) and stroke volume (4.3 +/- 0.4 ml) were maintained, whereas end-diastolic volume (7.9 +/- 1.3 ml) did not change significantly during this period. RV systolic function improved substantially; the end-systolic pressure-volume relation shifted leftward indicated by a significantly decreased volume intercept (up to 70%), together with a slightly increased slope. In this newborn lamb model, maintenance of CO during increased RV afterload is not obtained by an increased end-diastolic volume (Frank-Starling mechanism). Instead, the RV maintains its output by improving contractile performance through homeometric autoregulation.

Animals↗

Influence of inhibition of nitric oxide synthesis on cardiac function in the newborn lamb after hypoxic-ischemic injury.

The aim of the present study was to investigate the effect of immediate post-hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(omega)-nitro-L-arginine (NLA) on cardiac function and reactive oxygen species production. Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5 received 10 mg NLA/kg, 4 40 mg NLA/kg and 6 a placebo. Left ventricular (LV) contractility, cardiac output (CO), non-protein-bound iron (NPBI), ratio of reduced/oxidized ascorbic acid, alpha-tocopherol, sulfhydryl groups and malondialdehyde were measured before and 15, 60 and 120 min after resuscitation. There was a significant decrease in CO in all 3 groups at 60 min post-HI (p < 0.05). Reactive oxygen species production was also highest at 60 min post-HI (significantly increased NPBI and decrease in sulfhydryl groups in control lambs; p < 0.05). These results suggest neither a positive nor a negative effect of nitric oxide synthesis inhibition on post-HI myocardial performance but may suggest a positive effect of NLA on reactive oxygen species-mediated post-HI damage.

Animals↗

Right ventricular function in respiratory distress syndrome and subsequent partial liquid ventilation. Homeometric autoregulation in the right ventricle of the newborn animal.

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.

Animals↗

Pretreatment with allopurinol in cardiac hypoxic-ischemic reperfusion injury in newborn lambs exerts its beneficial effect through afterload reduction.

The aim of this study was to determine whether allopurinol (ALLO) reduces reperfusion injury inflicted upon the heart resulting from excess production of free oxygen radicals after hypoxia and ischemia (HI) in newborn animals. We, therefore, produced severe HI in 13 newborn lambs by low O2-ventilation and blood volume reduction. One hour before HI seven lambs received ALLO (20 mg/kg i.v.), six received a placebo (CONT). Cardiac function and hemodynamic parameters were assessed by sequential measurement of left ventricular (LV) contractility through the end-systolic pressure-volume relation (ESPVR) using the conductance catheter method. Stroke volume (SV), cardiac output (CO), and aortic pressure (Pao) were measured and ejection fraction and total peripheral resistance (TPR) were calculated before HI, upon resuscitation (UR), and at 60 and 120 min post-HI. To estimate the effect of ALLO on redox status and anti-oxidative capacity, we measured concentrations of uric acid, sulfhydryl (SH), malondialdehyde (MDA), ascorbic acid (AA), and dehydroxylated ascorbic acid (DHAA) in plasma obtained from the coronary sinus and calculated the AA/DHAA ratio. Compared to CONT lambs, TPR in ALLO treated lambs decreased significantly, accompanied by a rise in CO and SV. ALLO did not affect myocardial contractility, because the ESPVR showed no significant differences between groups. AA/DHAA and SH showed a significant decrease in ALLO animals vs pre-HI, but not in CONT animals. Uric acid was significantly decreased in ALLO as compared to pre-HI and CONT animals. MDA was significantly increased in CONT animals at 15 min post-HI as compared to pre-HI, whereas in ALLO animals MDA showed a significant increase at 120 min post-HI vs CONT. We conclude that pretreatment with ALLO has a beneficial effect on the pump function by afterload reduction but not by changes in contractility. Furthermore, ALLO inhibited uric acid formation with a consequent decrease in anti-oxidative capacity.

Allopurinol↗

Right ventricular systolic function and ventricular interaction during acute embolisation of the left anterior descending coronary artery in sheep.

OBJECTIVE: Regional LV ischemia involving the septum affects LV systolic function and geometry. We investigated the effects of these changes on RV function and geometry. METHODS: In six closed-chest sheep end-systolic pressure-volume relationships (ESPVRs) were constructed from ventricular volumes, measured with magnetic resonance imaging (MRI) and matching intraventricular pressures, before and after selective embolisation of the left anterior descending coronary artery (LAD). The extent of myocardial ischemia was assessed post-mortem by coronary perfusion with Evans-Blue. Alterations in septal geometry were studied by measuring the curvature, segmental length and thickness of the septum in two midventricular (short-axis) MRI slices before and during ischemia. From these data, changes in LV and RV free wall segmental lengths were calculated. RESULTS: Selective embolisation of the LAD resulted in left ventricular ischemia (15 +/- 2.1% of the total LV) with 23% of the septum involved. Stroke volume did not change significantly, while LV systolic pressure decreased by 24 mmHg (p < 0.05). Although RV systolic function decreased to a significantly lesser extent than LV function (p < 0.01), systolic function of both ventricles diminished significantly as indicated by substantial rightward shifts of the ESPVRs: 121% for LV and 41% for RV (both p < 0.01). At mid-ventricular level and end-systole, the septum showed significant increases in its radius of curvature and segmental length (both p < 0.05), and a significant wall thinning (p < 0.01). Calculated end-systolic lengths of LV and RV free walls also increased, by 57 and 14% respectively. CONCLUSIONS: LAD embolisation not only results in a significantly diminished LV systolic function but also causes RV systolic function to decline significantly. Regional dysfunction by necessity entails global dysfunction as well. Analysis of ventricular geometry reveals that both the septum and the RV free wall increase their length, which plays an important role in the pathophysiology of diminished RV systolic function concomitant with reduced LV function.

Animals↗

Electrocortical brain activity during hypoxia and hypotension in anesthetized newborn lambs.

Blood gas and blood pressure disturbances do influence cerebral blood flow in newborns. To what extent cerebral blood flow changes affect electrocortical brain activity remains uncertain. We studied the effect of severe hypoxia and hemorrhagic hypotension on carotid artery blood flow and electrocortical brain activity in newborn anesthetized lambs. During hypoxia carotid artery blood flow increased significantly, whereas electrocortical brain activity remained unchanged. The hemorrhagic hypotension study showed that the lower limit of the autoregulatory ability of the cerebral vascular bed was 60 mmHg. Electrocortical brain activity however remained stable until mean aortic pressure had dropped below 30 mmHg, carotid artery blood flow below 10.6 ml/kg/min, and cerebral oxygen delivery below 1.4 ml/kg/min.

Anesthesia↗

Effect of exchange transfusion on brain perfusion and electrocortical brain activity in newborn lambs.

Changes in brain perfusion (using ultrasonic-determined changes in carotid artery blood flow: Qcar) and electrocortical brain activity (ECBA, obtained by a Lectromed cerebral function monitor) were studied during exchange transfusion using the push-pull method in the newborn lamb. Changes in mean arterial blood pressure (MABP), Qcar, heart rate (HR), and ECBA were observed during all exchange transfusions: MABP, Qcar, and ECBA decreased during the withdrawal period and increased during the infusion period, whereas HR showed the opposite phenomenon. Changes in ECBA appeared to be primarily associated with changes in brain perfusion (p < 0.05). These changes in brain perfusion were, however, caused by changes in MABP (p < 0.0001). We concluded that exchange transfusions caused moderate changes in brain perfusion, however changes in ECBA appeared to be very small, and have probably no clinical importance.

Animals↗

Effect of deferoxamine on post-hypoxic-ischemic reperfusion injury of the newborn lamb heart.

UNLABELLED: Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (Ees) and volume intercept of the end-systolic P-V relationship (V10). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither Ees nor EF changed significantly in either group, the volume intercept V10 in the DFO-treated group was significantly smaller (0.25 +/- 0.03 vs. 0.70 +/- 0.09, p < 0.05), whereas SV was larger (3.6 +/- 0.6 vs. 2.2 +/- 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. IN CONCLUSION: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.

Animals↗

Effects of critical coronary stenosis on global systolic left ventricular function quantified by pressure-volume relations during dobutamine stress in the canine heart.

OBJECTIVES: In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress. BACKGROUND: The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented. METHODS: In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 microg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX vs. end-diastolic volume (dP/dtMAX - V(ED)) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion. RESULTS: In control, dobutamine gradually increased heart rate up to 20 microg/kg/min, the inotropic effect blunted at 15 microg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 microg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX - V(ED), showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 microg/kg/min; the differences were largest at 15 microg/kg/min. CONCLUSIONS: Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 microg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 microg/kg/min and higher.

Animals↗

The effect of antioxidative combination therapy on post hypoxic-ischemic perfusion, metabolism, and electrical activity of the newborn brain.

Reoxygenation and reperfusion after severe hypoxia and ischemia (HI) contribute substantially to birth asphyxia-related brain injury. Excess production of free radicals via metabolization of arachidonic acid, xanthine oxidase, and non-protein-bound iron play an important role. Cerebral reperfusion injury is characterized by a decrease in perfusion, oxygen consumption, and electrical activity of the brain. Reduction of free radical production may attenuate these features. We therefore induced severe HI in 35 newborn lambs, and upon reperfusion the lambs received a placebo [control (CONT), n = 7], the cyclooxygenase inhibitor indomethacin (INDO, 0.3 mg/kg/i.v., n = 7), the xanthine oxidase inhibitor allopurinol (ALLO, 20 mg/kg/i.v., n = 7), the iron chelator deferoxamine (DFO, 2.5 mg/kg/i.v., n = 7), or a combination of these drugs (COMB, n = 7). In each group changes (%) from pre-HI values were investigated for brain perfusion [measured by carotid artery flow (Qcar, mL/min)], (relative) cerebral O2 metabolism (CMR(O2)), and electrocortical brain activity (ECBA, microV) at 15, 60, 120, and 180 min post-HI. Qcar decreased significantly at 120 and 180 min post-HI in CONT (p < 0.05), but not in INDO, ALLO, DFO, and COMB groups. CMR(O2) decreased significantly in CONT at 60 min post-HI (p < 0.05), remained stable in DFO and INDO, and was significantly higher in ALLO and COMB (p < 0.05) at 120 and 180 min post-HI. ECBA was significantly lower in CONT during the whole post-HI period (p < 0.05), ECBA in INDO and COMB were significantly decreased at 60 and 120 min post-HI (p < 0.05), but recovered afterward, whereas DFO and ALLO remained stable during the post-HI period. In conclusion preservation of Qcar and CMR(O2), and recovery of ECBA occurred after treatment with INDO, ALLO, and DFO; combination of these drugs did not have an additional positive effect.

Allopurinol↗

Acute elevation of coronary venous pressure does not affect left ventricular contractility in the normal and stressed swine heart: implications for the Fontan operation.

OBJECTIVE: After the Fontan operation the right atrium and, thus, the coronary sinus are connected to the pulmonary arterial system, which causes the coronary venous pressure to increase. We investigated the acute effects of elevation of coronary venous pressure on baseline hemodynamics, coronary venous flow, and left ventricular contractility. METHODS: In acutely instrumented pigs, during complete right heart bypass and during constant cardiac output, pressure in the right atrium, right ventricle, and coronary sinus was altered by a height-adjustable reservoir. At various levels of coronary venous pressure (up to 4 kPa or up to 30 mm Hg), flow from the reservoir was measured and left ventricular hemodynamics and contractility were measured from catheter-derived left ventricular pressure and (conductance) volume data. Contractility of the left ventricle was assessed by the end-systolic pressure-volume relationship derived during an unloading intervention by adjusting the bypass pump speed. RESULTS: Left ventricular end-diastolic pressure increased slightly (about 5%) with each kilopascal increase in coronary venous pressure, most likely related to diastolic ventricular interaction. No other changes in hemodynamic parameters occurred. Neither coronary venous flow nor left ventricular contractility was influenced by changes in coronary venous pressure. Imposing myocardial stress with dobutamine, 10 microg/kg per minute, did not change these findings. CONCLUSION: Increasing coronary venous pressure to 4 kPa in the intact circulation with intact autoregulation does not affect coronary flow or left ventricular contractility. We found no experimental evidence for the usefulness of diversion of the coronary sinus to the left atrium during Fontan-type operations

Adrenergic beta-Agonists↗

Effect of post-hypoxic-ischemic inhibition of nitric oxide synthesis on cerebral blood flow, metabolism and electrocortical brain activity in newborn lambs.

Since an excessive production of nitric oxide upon reperfusion/reoxygenation may play an important role in post-hypoxic-ischemic (HI) brain injury, we investigated whether immediate post-HI blockade of nitric oxide synthesis by N-omega-nitro-L-arginine (NLA) may reduce this injury. In 18 newborn lambs, subjected to severe HI, changes from pre-HI values were measured for carotid blood flow (Qcar [ml/min]) as a measure of changes in brain blood flow, (relative) cerebral metabolic rate of oxygen (CMRO2), and electrocortical brain activity (ECBA) at 15, 60, 120 and 180 min after HI. Upon completion of HI, at the onset of reperfusion and reoxygenation, 6 lambs received a placebo (control group), 6 low-dose NLA (10 mg/kg i.v., NLA-10 group), and 6 high-dose NLA (40 mg/kg i.v., NLA-40 group). Histological damage to cerebellar Purkinje cells was assessed after termination of the experiment. Only the control group showed a distinct initial post-HI cerebral hyperperfusion. From 60 min after HI onward Qcar was decreased to about 75% of pre-HI Qcar in all 3 groups, although none of these changes in Qcar reached statistical significance. Despite the decreased Qcar in all 3 groups, only the control group showed a significantly decreased CMRO2. ECBA and its bandwidth decreased in all groups, but only recovered in the NLA-10 group 180 min after HI. The brain to body mass ratio (%) and percentage necrotic Purkinje cells were, respectively: 15.3 +/- 0.8 and 56 +/- 10 (control group); 12.5 +/- 1.2 and 36 +/- 9 (NLA-10 group), and 11.3 +/- 1.0 (p < 0.05 vs. the control group) and 35 +/- 14 (NLA-40 group). Since post-HI reperfusion injury of the brain has been characterized by a decreased CMRO2 and electrical brain activity, we conclude that preservation of CMRO2 in both NLA groups, but a recovery of ECBA and its bandwidth only in the NLA-10 group, suggests that NLA, and especially low-dose NLA, may reduce post-HI brain injury.

Animals↗

Nitric oxide inhibition after hypoxia-ischemia elevates pulmonary arterial pressure and increases oxygen need.

Inhibition of nitric oxide (NO) production may reduce post-hypoxic-ischemic (HI) neonatal brain damage, but may also induce pulmonary hypertension by inhibiting endogenous NO production in the pulmonary vascular bed. The aim of this study was to evaluate the effect of nitric oxide inhibition on pulmonary artery pressure and oxygen need after hypoxic ischemia. Severe HI was produced in 18 newborn lambs. After completion of HI the lambs were divided into three groups of 6 animals receiving either placebo (Cont), low dose N omega-nitro-L-arginine (10 mg/kg i.v., NLA-10) or high dose (40 mg/kg i.v., NLA-40) to block NO production. Pulmonary artery pressure (Pap), aortic pressure, blood gases, inspiratory oxygen concentration and ventilator settings were recorded before and 15, 60, 120 and 180 min after HI. Mean Pap rose initially significantly as compared to baseline in all groups at 15 min post-HI, decreased to normal in Cont but not in treated animals; 180 min post-HI mean Pap was significantly higher in both treated groups as compared to control (NLA-10: 32 mm Hg, NLA-40: 34 mm Hg, Cont: 25 mm Hg, p < 0.05 for NLA-10 and NLA-40 vs. Cont). Moreover, in both NLA-treated groups the oxygenation index was significantly elevated 120 and 180 min post-HI as compared to those of the Cont group. NO synthase inhibition after HI causes a prolonged increase in pulmonary artery pressure leading to a higher oxygen need.

Animals↗

Oxidative stress during post-hypoxic-ischemic reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition.

Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e. iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), alpha-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.) N omega-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/i.v.; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p < 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI, p < 0.05), but remained stable in NLA lambs. alpha-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 +/- 0.9 versus 4.2 +/- 0.7 microM (NLA-40), p < 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 +/- 017 versus 0.44 +/- 0.05 microM (NLA-40), p < 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity.

Animals↗

Magnetic resonance imaging analysis of left ventricular pressure-volume relations: validation with the conductance method at rest and during dobutamine stress.

The accuracy of magnetic resonance (MR) imaging was assessed for in vivo measurement of the ventricular end-systolic pressure-volume relation (ESPVR) and preload recruitable stroke work (PRSW). The conductance catheter was used as reference. In 10 pigs, ventricular volumes were measured with both methods under different loading conditions at two levels of contractility. Increased contractility resulted in a significant leftward shift of the ESPVR and PRSW for both methods. The magnitude of these shifts was on average similar for the two methods; MR imaging, 6.9 ml for ESPVR, 9.3 ml for PRSW; and the conductance catheter, 7.4 ml for ESPVR, 9.1 ml for PRSW. It was concluded that MR imaging may be used for in vivo analysis of pressure-volume relations, and that its sensitivity for detecting contractility changes is similar to that of the conductance catheter method.

Animals↗

Interaction between afterload and contractility in the newborn heart: evidence of homeometric autoregulation in the intact circulation.

OBJECTIVES: We undertook the present study to determine whether afterload and contractility interact in the hearts of newborn lambs. We specifically investigated whether stepwise increases in afterload increase contractility. BACKGROUND: Several studies in the isolated and intact adult dog heart have shown that afterload and contractility are not independent determinants of cardiac performance; rather, they interact. Afterload and contractility are unlikely to interact in the newborn heart because the factors that may mediate the interaction in the adult are missing in the newborn. METHODS: We measured contractility at different steady state levels of afterload in seven newborn lambs under complete anesthesia. Contractility was measured by three different indexes: end-systolic pressure-volume relations (slope and volume position); preload-corrected first derivative of left ventricular pressure (dP/dtmax); and preload-corrected stroke work. Left ventricular pressure and volume were measured with a micromanometer and conductance catheter, respectively. Preload and afterload were manipulated by inflating or deflating a balloon catheter in the inferior vena cava and descending thoracic aorta, respectively. Data are expressed as mean value +/- 1 SD. RESULTS: Stepwise increases in afterload increased contractility, independent of which of the three indexes was used. The slope of the end-systolic pressure-volume relation increased from a mean baseline value of 4.44 +/- 2.43 to 6.69 +/- 2.89 kPa/ml at the highest level of afterload. Concomitantly, volume at 14 kPa of the end-systolic pressure-volume relation decreased from 3.34 +/- 1.52 ml at baseline to 1.12 +/- 0.83 ml at the highest afterload. The other two indexes showed qualitatively similar changes. Beats selected from unloading interventions on the basis of the same end-diastolic volume for each level of afterload showed no difference in stroke volume. CONCLUSIONS: This study in newborn lambs demonstrates that stepwise increases in afterload increase contractility considerably and that this enables the heart to maintain stroke volume at different levels of afterload. This forms direct evidence for the existence of homeometric autoregulation in the intact newborn heart.

Analysis of Variance↗

Comparison between regional myocardial perfusion reserve and coronary flow reserve in the canine heart.

Diameter stenosis and flow reserve are indices of morphological and functional severity of coronary artery stenosis. Flow reserve can be determined at coronary arterial or at myocardial level. In the presence of functional collateral circulation, coronary flow reserve and myocardial perfusion reserve may differ. We studied coronary flow, coronary flow reserve and myocardial perfusion reserve in an open chest dog model with intact collateral circulation, before and after induction of coronary artery stenosis. Coronary flow was determined with perivascular ultrasonic flow probes and myocardial perfusion reserve from digital angiographic images, in the stenotic as well as the adjacent non-stenotic coronary arteries. Before induction of a stenosis, a significant correlation existed between coronary flow reserve and myocardial perfusion reserve of the left anterior descending (r = 0.59; P < 0.005) and the left circumflex arteries (r = 0.84, P < 0.005). In stenotic arteries, coronary flow reserve and myocardial perfusion reserve decreased significantly (P < 0.005), but in the adjacent non-stenotic arteries coronary flow reserve was not affected. Myocardial perfusion reserve in the non-stenotic adjacent left anterior descending artery decreased significantly (P < 0.05) and no correlation was found between coronary flow reserve and myocardial perfusion reserve, whereas in the adjacent non-stenotic left circumflex artery there was no statistically significant decrease (4.1 +/- 1.6 --> 3.5 +/- 1.4) but there was a good correlation between coronary flow reserve and myocardial perfusion reserve (r = 0.85; P < 0.005). This study demonstrates that, in the presence of a stenosis and functioning collateral circulation, coronary flow reserve is not a reliable predictor of myocardial perfusion reserve; both parameters provide mutually complementary information.

Angiography, Digital Subtraction↗

Cardiovascular MR imaging: pressure-gating using the arterial pressure signal from a conventional ferromagnetic micromanometer-tip catheter.

We used the arterial pressure wave as a reliable trigger to synchronize MR imaging to the cardiac cycle. Pressure readings and MR images remained undistorted using a conventional ferromagnetic micromanometer-tip catheter. As a safe alternative to triggering to ventricular pressure, this approach allows varying the time relation between the trigger and the cardiac cycle while maintaining the advantages of pressure-gating.

Animals↗