Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry?

BACKGROUND: Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. METHODS: Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation ≤30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT≥166 s; MCF≤43 mm) to detect platelet function were determined. RESULTS: The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80-0.97) and 0.86 (0.77-0.96), respectively] but not immediately after CPB [0.64 (0.48-0.79) and 0.67 (0.52-0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37-0.69) and 0.60 (0.44-0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF≤43 mm; 80 and 100% for CFT≥166 s) but markedly lower after surgery. CONCLUSION: In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB.

Platelet count and function in paediatric cardiac surgery: a prospective observational study.

BACKGROUND: Platelet deficiency, impaired platelet function, or both increase the risk of bleeding complications. We assessed platelet count and function during and after paediatric cardiac surgery. Secondary aims included the effect of modified ultrafiltration, identification of factors associated with platelet dysfunction, and to assess associations between platelet function and transfusion requirements. METHODS: Fifty-seven patients were included in a prospective observational study. Platelet count and platelet function (multiple-electrode impedance aggregometry) were analysed before and during cardiopulmonary bypass (CPB), after modified ultrafiltration, on arrival at the intensive care unit, and on the first postoperative day. Intraoperative transfusions of blood products were registered. RESULTS: Both platelet count and platelet aggregation were markedly reduced during surgery with the greatest reduction at the end of CPB. On postoperative day 1, platelet count was still reduced by 50%, while platelet aggregation had returned to-or above-preoperative levels. There were only moderate correlations between platelet count and platelet aggregation. Modified ultrafiltration had no significant influence on platelet count or aggregation. Young age, low weight, and long operation time were associated with poor platelet aggregation during surgery, while young age, low weight, high preoperative haemoglobin levels, and low preoperative platelet count were associated with poor aggregation after operation. Patients with impaired platelet function during CPB had markedly increased intraoperative transfusion requirements. CONCLUSIONS: Platelet count and platelet aggregation are markedly reduced during and immediately after paediatric cardiac surgery, especially in neonates. The recovery in aggregation is faster than that in platelet count. Intraoperative platelet dysfunction is associated with increased transfusion requirements.

Creation and enlargement of atrial defects in congenital heart disease.

Transcatheter creation and enlargement of interatrial defects (IAD) may improve hemodynamics; however, procedural outcomes have not been well defined. Hospital records were reviewed for children who underwent percutaneous procedures to create and enlarge an IAD and were grouped as follows: (1) right and (2) left heart obstructive lesions, (3) left atrial (LA) decompression during left heart assist, (4) failing Fontan circulation, and (5) miscellaneous. Forty-five children (mean age, 3.4 +/- 4.7 years; 30 (67%) male) were identified. In group 1 (n = 6), all achieved endpoints of right atrial (RA) decompression (n = 2), improved left ventricular filling (n = 3), or improved arterial saturations (n = 1). In group 2 (n = 18), mean LA pressure decreased (21 +/- 6 to 13 +/- 5 mmHg, p < 0.001) and arterial saturations increased (61 +/- 13% to 78 +/- 11%, p < 0.001). All except 2 patients achieved definitive repair, further palliation (n = 9), or heart transplantation (HTX) (n = 7). In group 3 (n = 5), the LA was decompressed (21 to 13 mmHg, p = 0.03) in all, and all except 1 patient survived to HTX (n = 2) or full recovery (n = 2). In group 4 (n = 11), of 7 patients with a low cardiac output syndrome after surgery, despite improved atrial shunting, 3 died and 1 required a HTX. In group 5 (n = 5), RA decompression (n = 1) or improved arterial saturation (n = 4) was achieved in all. Overall, 5-year HTX free survival was 75%. Mechanical ventilation before the procedure (p < 0.001), the need for a blade septostomy (p = 0.002), and higher LA pressures after the procedure (p = 0.04) independently predicted mortality or the requirement for HTX. Transcatheter optimization of an atrial communication can help optimize treatment strategies and has a low procedural risk.

Increased left ventricular mass in obese adolescents.

AIMS: An increase of left ventricular mass (LVM) has been reported in obese adolescents in previous studies using echocardiography. The aim of our study was to determine the extent of the increase in LVM and correlation to other risk factors using cardiac magnetic resonance imaging in obese and lean adolescents. METHODS AND RESULTS: Nineteen obese and 20 lean adolescents were recruited. Following resting blood pressure measurements and blood sampling for insulin, triglycerides, and cholesterol levels, all subjects underwent cardiac magnetic resonance examination to assess LVM. LVM adjusted for body height was 16% greater in obese compared to lean adolescents (median 66 g/m, p = 0.0042). Obese subjects had higher resting systolic blood pressures than controls (median 115 vs. 110 mmHg, p = 0.0077) and higher fasting triglyceride and insulin levels. HDL-cholesterol levels were lower in the obese group compared with the lean group. CONCLUSIONS: Obese adolescents had a higher LVM than age-matched lean subjects, which correlated mainly with body mass index and systolic blood pressure. These findings add to the established cardiovascular risk profile of obese adolescents.

Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy.

AIM: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). METHODS: Blood samples for plasma P-BNP and P-ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non-parametric. RESULTS: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P-BNP and P-ANP were higher, 263 ng l(-1) (range 47.5-1300) and 303 ng l(-1) (range 168-466), than in those without CSHF, 12.3 ng l(-1) (range 4.8-30.8) and 42.9 ng l(-1) (range 13.7-189), respectively (p < 0.001, Mann-Whitney U-test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD. CONCLUSION: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.

Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings.

AIMS: To determine the frequency of cardiomyopathy in children with mitochondrial disease and describe their clinical course, prognosis and cardiological manifestations. METHODS AND RESULTS: Of 301 children with CNS and neuromuscular disease referred to our institution in 1984 to 1999, 101 had mitochondrial disease. Seventeen patients had cardiomyopathy, diagnosed by echo-Doppler investigations, all of the hypertrophic, non-obstructive type. The onset of symptomatic mitochondrial disease ranged from birth to 10 years of age. Eight children had cytochrome-c oxidase deficiency, while the remaining nine had various defects. Cardiomyopathy was diagnosed from birth to 27 years. Left ventricular posterior wall and septal thickness were both increased: z-scores +4.6+/-2.6 and +4.3+/-1.6 (mean+/-SD), respectively. The left ventricular diastolic diameter z-score, +1.3+/-3.4, and fractional shortening, 24+/-13%, displayed marked variations. Nine patients developed heart failure. Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency, and one patient underwent a heart transplantation. Mortality in children with mitochondrial disease was higher in those with cardiomyopathy (71%) than those without (26%) (P<0.001). CONCLUSIONS: In children with mitochondrial disease, cardiomyopathy was common (17%) and was associated with increased mortality. The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared to be particularly unfavorable.

Reversal of protein-losing enteropathy in a child with Fontan circulation is correlated with central venous pressure after heart transplantation.

We report on the reversal of protein-losing enteropathy (PLE) after heart transplantation (HTx) in a 10-yr-old boy with Fontan circulation, previously treated unsuccessfully with heparin for several months. The protein loss continued immediately after the Tx. During the following month, however, a gradual decrease in protein loss was observed, which correlated with a decrease in the inferior vena cava (IVC) pressure. The patient is doing well with a normal serum albumin level and a normal IVC pressure, 2 yr after Tx.

Interaction between the renin-angiotensin system and insulin-like growth factor I in aorto-caval fistula-induced cardiac hypertrophy in rats.

The effects of angiotensin converting enzyme inhibition and angiotensin II receptor blockade on the development of cardiac hypertrophy and myocardial insulin-like growth factor I (IGF-I) in volume overload were studied in male Wistar rats with aorto-caval fistulas (ACF). Rats were treated with ramipril (RAM, 3 mg kg(-1) day(-1)) for 4-20 days or losartan (LOS, 10 mg kg(-1) day(-1)) for 2-7 days. Myocardial IGF-I and IGF-I receptor (IGF-I-R) mRNA were determined by solution hybridization. ACF caused hypertrophy of left (LV) and right ventricles (RV). Hypertrophy appeared on day 2 and reached maximal values of +60% in LV and +75% in RV at day 12. Systolic blood pressure was initially reduced 15% but recovered by day 12. RAM abolished the recovery of blood pressure. Furthermore, RAM attenuated RV hypertrophy by 17% on day 7 and on day 20, RV weights were close to values found in controls. Beginning on day 9, RAM reduced LV weight back to control levels in parallel to blood pressure. In contrast, LOS affected neither RV nor LV hypertrophy. RV IGF-I mRNA increased 60-100% on day 7 alone in RV in ACF. RAM potentiated the increase in RV IGF-I to +400% and induced an increase in RV IGF-I-R mRNA on day 7 (+90%) in ACF. LOS did not affect RV IGF-I. Development of cardiac hypertrophy in ACF seemed independent of angiotensin II. RV hypertrophy was associated with activation of IGF-I independent of the renin-angiotensin system. IGF-I was further potentiated when development of hypertrophy was attenuated, possibly indicative of a greater urge for compensational growth in a relatively thinner and more volume-distended chamber.

Therapeutic, but not low-dose, angiotensin-converting enzyme inhibition causes regression of cardiovascular changes in spontaneously hypertensive rats.

Therapy with angiotensin II-converting enzyme (ACE) inhibitors has been suggested to prevent cardiovascular hypertrophy in hypertension even in doses that are subantihypertensive. We investigated the effects of two different ACE inhibitors on blood pressure and cardiovascular changes during as well as after discontinuation of treatment in spontaneously hypertensive rats (SHR). SHR were treated with either enalapril (ENA) or ramipril (RAM) from age 12 to age 20 weeks. Each drug was given in either an antihypertensive (ENA 15 mg center dot kg-1, RAM 3 mg center dot kg-1) or a subantihypertensive (ENA 50 mu g center dot kg-1, RAM 10 mu g center dot kg-1) dose. Mean arterial pressure (MAP) was reduced with antihypertensive doses of ENA (26%) as well as RAM (21%). Regression of cardiovascular changes occurred as reduction in left ventricular (LV) weight/body weight ratio (25 and 21% for ENA and RAM, respectively), reduction in perfusion pressure at maximal vasodilation of the perfused hindquarter (PPdil, 17 and 17%), and reduction in maximal developed pressure (PPmax, 13 and 17%). These effects partly persisted 10 weeks after treatment was discontinued. However, treatment with subantihypertensive doses of ENA and RAM had no effect on MAP, LV/body weight ratio, PPdil, or PPmax. Overall, regression of cardiovascular parameters correlated closely to the decrease in MAP. Similarly, no changes in MAP, LV weight/body weight ratio, PPdil, or PPmax were noted when young SHR were treated with subantihypertensive doses of RAM from age 6 to age 12 weeks, during which time hypertension becomes established. At doses having equal effects on blood pressure, plasma concentrations of RAM were considerably lower than those of ENA. Skeletal muscle concentrations were very low or undetectable in comparison to plasma concentrations for both drugs. Therefore, both RAM and ENA caused regression of cardiovascular changes that could be explained by a concomitant reduction in blood pressure. This regression persisted for a considerable time after discontinuation of treatment. On the other hand, no specific antitrophic effects in the absence of blood pressure reduction was evident with either drug. Furthermore, despite substantial differences in plasma concentrations, RAM, and ENA administered chronically appeared to affect cardiovascular parameters equally in the adult SHR.

Regional myosin heavy chain expression in volume and pressure overload induced cardiac hypertrophy.

Although the overall shift towards the V3 myosin heavy chain (MHC) has been shown to be associated with cardiac hypertrophy, quantitative evidence describing regional expression is sparse. The aim of this study was to compare and contrast the regional ventricular myosin isoform expression in two distinct haemodynamic states: pressure and volume overload. Volume overload was achieved using an aortocaval fistula (ACF) model and pressure overload by two-kidney-one-clip (2K1C) hypertension. A separate group (UC-2K1C) had the clip removed 1 week prior to investigation. Sham operated rats (SHAM) served as controls. All groups were studied 4 weeks after surgery. Ventricular tissue samples (approximately 50 mg) were taken from the walls of the right ventricle (RV), septum and left ventricular (LV) free wall. Tissue samples (excluding RV) were divided into endocardium and epicardium, and myosin expression was determined using polyacrylamide gel electrophoresis. Cardiac hypertrophy was substantial in both LV (1.7-fold) and RV (1.9-fold) in ACF rats. The 2K1C rats had similar LV enlargement (1.6-fold) whereas RV hypertrophy was not as great (1.2-fold). Blood pressure (BP) was increased 65% in 2K1C rats, whereas there was no change in ACF rats with respect to SHAM animals. After unclipping (UC-2K1C), LV hypertrophy and BP had returned towards control levels. In general, V3 MHC expression was associated with increasing LV hypertrophy in both 2K1C and ACF models. However, there was a marked endo-epi differential (1.5:1) in the LV free wall and septum of 2K1C rats. In contrast, in ACF rats there was no differential V3 MHC expression in the LV or septal tissue, i.e. expression was similar in both endo- and epi-samples. Elevated expression of V3 MHC persisted despite normotension and regression of cardiac hypertrophy in UC-2K1C rats. Taken together with published results demonstrating that relative transmural myocyte hypertrophy in ACF rats (endo > epi) is in contrast to that seen in 2K1C rats (epi > endo), the present findings reveal that regional V3 myosin expression represents a distinct adaptational component of the overall cardiac hypertrophic response in both volume and pressure overload.

Cardiac hypertrophy and related growth processes: the role of insulin-like growth factor-I.

For the heart and resistance vessels in general, increases in pressure load represent a major local stimulus for structural adaptation by elevating the wall tension against which cardiac and vascular smooth muscle contract. Under such conditions the wall thickness of the left ventricle and of the resistance vessels will increase, keeping wall tension per unit muscle layer (wall stress) normal. Alternatively, chronic volume overload and enhanced cardiac filling will induce a structurally based widening of the ventricular lumen. This pattern is associated with a corresponding increase in myocardial mass, so that the wall thickness to internal radius ratio remains more or less constant. A number of extrinsic influences such as the sympathetic nervous system, hormonal factors and growth factors, may superimpose their effects to modulate the final "trophic influence" on the cardiovascular system. Hyperactivity of the renin-angiotensin system, the sympathetic nervous system and various growth factors, have all been suggested to initiate cardiovascular growth in a way that is load-independent. The mechanisms involved in the conversion of a mechanical hypertrophic stimulus into an actual increase in tissue mass are likely to involve many substances and enzyme systems, including transcription factors, enzymes such as ornithine decarboxylase and various growth factors. The presence of the insulin-like growth factor-I (IGF-I) in the heart and vessels suggests a paracrine/autocrine role for this potent growth factor in the regulation of cardiovascular growth. The relationships between ornithine decarboxylase, cardiovascular hypertrophy and IGF-I gene expression are also reviewed.

Increased expression of growth hormone receptor mRNA and insulin-like growth factor-I mRNA in volume-overloaded hearts.

Recent results suggest that insulin-like growth factor-I (IGF-I) may be involved in the transition of a hemodynamic load into cardiac hypertrophy and that the expression of IGF-I seems to be coupled to increased wall stress. The present study investigated the role of growth hormone (GH) and IGF-I in myocardial hypertrophy induced by volume overload. An aortocaval fistula (ACF) was created in male Wistar rats, and experiments were performed 2, 4, and 7 days after the onset of volume overload. Right and left ventricular (RV and LV, respectively) myocardial expression of GH receptor mRNA and IGF-I mRNA were quantitated by a solution hybridization RNase protection assay. RV GH receptor mRNA content was elevated on the fourth and seventh days after the induction of the shunt, with peak levels (0.63 +/- 0.16 versus 0.14 +/- 0.03 amol/microgram DNA for the sham-operated animals; P < .01) after 4 days. Similarly, IGF-I mRNA was significantly increased in the RV of shunted animals (1.26 +/- 0.13 versus 0.56 +/- 0.05 amol/micrograms DNA; P < .01) 7 days after surgery. In the left ventricle, where systolic pressure was reduced in ACF rats, no differences could be detected in GH receptor and IGF-I mRNA content between ACF and sham-operated rats on any of the experimental days. There was no difference in the ratio of RV to LV weight during the experimental period. We have shown that the thin-walled right ventricle responds to volume overload with an increase of GH receptor mRNA content followed by elevated expression of IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial capillary diffusion capacity in rat hearts with cardiac hypertrophy due to pressure and volume overload.

The functional adaptation of the myocardial capillary bed in response to cardiac hypertrophy was studied in one volume overload (aortocaval fistula, ACF) and in one pressure overload model [left renal arterial stenosis, two-kidney, one-clip (2K,1C)]. Furthermore, a group where renal hypertension was reversed 1 wk before experimentation (UC-2K,1C) and a sham-operated (Sham) group were studied. Functional estimations of myocardial capillary diffusion capacity in terms of permeability surface area products (PS) per 100 g of myocardium were obtained by the single-injection indicator dilution technique in a Langendorff preparation. After 4 wk, ACF hearts, with 72% hypertrophy and normal minimal coronary vascular resistance (CVR), displayed an unchanged diffusion capacity, i.e., PS for Cr-EDTA and vitamin B12. This indicates a structural out-growth of the coronary vascular bed to match the increased demand of the tissue. 2K,1C hearts with marked elevations of minimal coronary vascular resistance and left ventricular hypertrophy (65%) showed higher PS values than Sham, implying that diffusion capacity was enhanced despite structural coronary vascular changes. These changes were completely reversed in UC-2K,1C. Thus the present data imply that myocardial capillary diffusion capacity was well maintained in volume overloaded cardiac hypertrophy and in contrast with earlier morphometric estimations, even enhanced in pressure overload hypertrophy.

Changes in myocardial capillary diffusion capacity during infusion of vasoactive drugs.

The present study investigated how variations in coronary vascular resistance and metabolic demand affected myocardial capillary diffusion capacity. Hearts from Wistar rats were perfused with Krebs-Henseleit-albumin buffer in a Langendorff preparation, where heart rate (HR), contractility (dP/dtmax) and myocardial oxygen consumption (MVO2) were recorded continuously. Myocardial capillary diffusion capacity was measured as the permeability surface area product (PS) for Cr-EDTA and vitamin B12 by the single injection colorimetric indicator dilution method. After base-line recordings without drugs, angiotensin II+Arginine-vasopressin was infused, which increased coronary vascular resistance by 90%, stimulated HR by 11%, decreased dP/dtmax by 21% and reduced MVO2 by 4%. PSCr-EDTA and PSB12 decreased by 24 and 27%, respectively, leaving the ratio PSCr-EDTA/PSB12 unchanged indicating unaltered capillary permeability. Moreover, the reductions in MVO2 and PS correlated significantly. During vasodilation: (1) nitroprusside-NA stimulated HR by 7% and decreased dP/dtmax by 14%; (2) adenosine reduced dP/dtmax by 37% and decreased MVO2 by 9%; and (3) isoproterenol increased HR, dP/dtmax and MVO2 by 53, 76 and 9%, respectively. However, all three vasodilators reduced PSCr-EDTA and PSB12 in parallel by 7-25% leaving PSCR-EDTA/PSB12 unchanged. Thus, maximal estimated diffusion capacities were obtained during spontaneous coronary vascular tone, most likely reflecting maximal capillary recruitment in the Krebs-Henseleit-albumin perfused heart. The derecruiting effects of the vasoconstrictors were partly overridden by metabolic factors, while the reductions of PS after vasodilation more likely were due to increased heterogeneity in coronary flow.

Capillary diffusion capacity for Cr-EDTA and cyanocobalamine in spontaneously beating rat hearts.

In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr-EDTA (mol. wt = 341) and cyanocobalamine (vitamin B12, mol. wt = 135) was determined in spontaneously beating Langendorff-perfused rat hearts over a wide range of coronary flow rates (700-3000 ml min-1 100 g-1). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 +/- 33 and 220 +/- 22 ml min-1 100 g-1 for Cr-EDTA and vitamin B12 respectively at the highest flow (2917 +/- 74 ml min-1 100 g-1). The vasculature of the heart was found to be highly heterogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of 'equivalent pore radius' was obtained from the ratio PSCr-EDTA/PSB12, which was 2.61 +/- 0.15 demonstrating a marked restriction to diffusion corresponding to a pore radius of 51 (41-75) A. This value is similar to that from skeletal muscle determined by the same method while PS-values are 40-45 times higher in the heart (Haraldsson & Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3-fold increase in the density of pores available for diffusion in the myocardium, compared to skeletal muscle.

Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats.

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.

Influence of early antihypertensive treatment on vascular and cardiac design in SHR with and without renal hypertension.

The present study was designed to explore to what extent pressure reduction by antihypertensive therapy and pressure elevation by renal hypertension are able to affect structural vascular and cardiac changes in young spontaneously hypertensive rats (SHR). Pressure elevation in SHR was induced by means of superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13 weeks of age in both clipped and unclipped SHR. Vascular structure of the skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation and left ventricular dimensions were calculated from pressure-volume relationships of isolated hearts arrested in diastole. Induction of renal hypertension in SHR resulted, besides augmentation of arterial pressure in a marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness to internal radius ratio. Likewise, in renal hypertensive SHR, a structural adaptation of the skeletal muscle vascular bed occurred, reflected as elevations of minimal vascular resistance and maximal generated perfusion pressure. Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented mean arterial pressure from increasing further in SHR, and in SHR with superimposed renal hypertension by approximately 15% (p < 0.001 for both). In renal hypertensive SHR, felodipine partly prevented the development of exaggerated structural changes, both in the heart and in the skeletal muscle vascular bed, as reflected by reduced wall thickness to internal radius ratio and reduced minimal vascular resistance by 22% and maximal pressure response by 10% respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular insulin-like growth factor I increases in early renal hypertension.

Increasing interest has been directed toward the possible role of trophically acting molecules as modulators or initiators, or both, of myocardial hypertrophy. The aim of the present study was to investigate the possible role of one such molecule, namely, insulin-like growth factor I, in myocardial hypertrophy developed in response to renal artery stenosis. Two-kidney, one clip Goldblatt hypertension was induced in Wistar rats weighing 180 g, and sham-operated animals were used as controls. Blood pressure was increased as early as 2 days after clipping (133 +/- 4 versus 116 +/- 4 mm Hg, p less than 0.05), and the increase persisted 4 and 7 days after clipping (148 +/- 6 versus 129 +/- 3 mm Hg, p less than 0.01 and 171 +/- 5 versus 139 +/- 3 mm Hg, p less than 0.01, respectively). Left ventricular weight followed a similar pattern (373 +/- 7 versus 350 +/- 8 mg, NS, 415 +/- 11 versus 386 +/- 9 mg, p less than 0.01, and 466 +/- 11 versus 391 +/- 10 mg, p less than 0.01 at 2, 4, and 7 days after clipping, respectively), but no changes in body weight between the groups were observed. Insulin-like growth factor I messenger RNA (mRNA) was quantified using a solution hybridization assay. After 4 days of renal hypertension, there was a significant increase in left ventricular insulin-like growth factor I mRNA (2.0 x 10(-18) +/- 0.48 x 10(-18) versus 0.4 x 10(-18) +/- 0.07 x 10(-18) mol.microgram DNA-1), which was no longer detectable 7 days after clipping.(ABSTRACT TRUNCATED AT 250 WORDS)