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B R Winkelmann

Publications and source records attributed to B R Winkelmann.

At least 19 recordsLinked to original sources
PubMed2002

Prospective cross-sectional study of haemostatic factors in patients with and without coronary artery disease.

The role of haemostatic factors for arterial thrombosis, especially the prevalence of activated protein C (APC) resistance in patients with coronary artery disease (CAD), is controversial. Between November 1996 and August 1997, 665 patients were analyzed. Diagnosis of CAD was confirmed by coronary angiography, exclusion of CAD was accepted in the presence of negative stress testing or a negative coronary angiography. CAD was present in 370 (56%) and excluded in 295 (44%) patients. Patients with CAD were older (64 +/- 9.2 versus 57.7 +/- 16 years; P <or= 0.001), more often male [74.1 versus 48.5%; odds ratio (OR) = 3.0, 95% confidence interval (CI) = 2.2-4.2] and had a higher body mass index (27.2 +/- 3.6 versus 26 +/- 4.3; P <or= 0.001). Most conventional risk factors showed a higher prevalence in patients with CAD. An APC ratio < 2.0 showed a tendency towards a higher prevalence in patients with CAD (10.5 versus 6.4%; OR = 1.7, 95% CI = 1.0-3.0). This difference was significant in men (11.7 versus 4.2%; OR = 3.0, 95% CI = 1.3-7.1), but not in women (7.3 versus 8.6%; OR = 0.8, 95% CI = 0.3-2.2). Multiple logistic regression analysis showed an independent association of the presence of CAD with age, male gender, current smoking, arterial hypertension, lipoprotein(a) levels and an APC ratio < 2.0 (OR = 2.87, 95% CI = 1.08-8.12). APC resistance with an APC ratio < 2.0 was the only haemostatic factor that was independently associated with the presence of CAD. This association was significant only for men. It may indicate a contribution of the APC resistance to the development of CAD, which has to be proven by the follow-up.

Aged↗
PubMed2002

Acute myocardial infarction in a young South African Indian-based population: patient characteristics on admission and gender-specific risk factor prevalence.

BACKGROUND: Myocardial infarction (MI) is a complex disease caused by interaction of a number of genetic and environmental factors. This disease has reached epidemic proportions in South African Indian descendants. The aim of this study was to survey the prevalence of coronary heart disease risk factors in a sub-group of young Indian patients (< or = 45 years) who presented to the Coronary Care Unit at the R. K. Khan Hospital in Durban, a major referral centre for patients with acute MI in the province of Natal. METHODS AND RESULTS: A total of 245 patients < or = 45 years of age were recruited from patients consecutively admitted to the Coronary Care Unit at the R. K. Khan Hospital, Durban, KwaZulu Natal, South Africa between 1996 and 1999 with a diagnosis of acute MI. All patients were of Indian origin living in the Durban area in the province of KwaZulu-Natal. Demographic and risk factor data were obtained from all patients and included anthropometric measures, family history and the traditional cardiovascular risk factor assessment (smoking, lipids, hypertension, and diabetes mellitus). Clinical data included in-hospital presentation, management and complications and angiographic classification of coronary atherosclerosis. The most prevalent risk factors were previous: smoking (74%), and hypertriglyceridaemia (54%). Only 14% of the population presenting with an acute MI were women. Smoking was more common among men (81%) than in women (35%). Abnormal high density lipoprotein (HDL) cholesterol levels were detected in 38% of the patients with a dear gender difference: 43% and 9%, in men and women, respectively. In contrast hypertension was more prevalent in young women with MI than in men: 38% and 19%, respectively. Coronary angiography was performed in 79 patients on admission; a single vessel stenosis was found in 28%, two vessel disease in 20% and triple vessel disease in 52%, respectively. On admission, 92% of patients were in Killip class I. Overt heart failure and cardiogenic shock were uncommon and were seen in 3.3% and 0.8%, respectively. Patients who received thrombolytic therapy had fewer complications (8%) compared to those who did not (11%). However, the difference towards a benefit of thrombolysis did not reach significance. Recurrent angina (6%) was the commonest complication, while ventricular arrhythmias were observed in 2% of patients. There was a strong familial link: 54% of the patients had a family background of coronary heart disease (CHD) while 42% and 41% had family members who suffered from diabetes mellitus and hypertension, respectively. CONCLUSION: Smoking and dyslipidaemia (predominantly hypertriglyceridaemia, and low HDL-cholesterol) were the most common cardiovascular risk factors of MI in young South African Indians. A strong familial link was observed not only for a history of CHD/MI, but also for hypertension and diabetes mellitus, supporting a genetic basis for the development of premature CHD. Therefore, further analysis of potential genetic factors such as variance of genes involved in vascular homeostasis, haemostatic factors, lipid metabolism and other metabolic factors seems warranted.

Adult↗
PubMed2001

[Gene polymorphisms of hemostasis and coronary risk].

Hemostatic disorders are substantially involved in the pathogenesis of coronary heart disease and acute coronary syndromes. In addition to biochemical markers, gene polymorphisms of hemostasis have been intensively studied in terms of their association with coronary risk. These include polymorphisms of the genes of platelet glycoproteins, fibrinogen, prothrombin, factors V, VIII and XIII, plasminogen activator inhibitor-1 and tissue-type plasminogen activator. An association of a certain gene polymorphism with an increased coronary risk has usually been demonstrated in retrospective case-control studies. However, numerous clinical studies have not yet been able to identify any of these polymorphisms as unequivocal risk factors of coronary heart disease or acute coronary syndromes. These inconsistencies are mainly due to the complexity of the pathogenesis of coronary heart disease and the minor contribution of a single polymorphism to total coronary risk. This review reports on essential requirements of future studies as a prerequisite to improve our understanding of the genetic basis of coronary heart disease.

Blood Coagulation Factors↗
PubMed2001

Genomics and large scale phenotypic databases.

Progress in the development of molecular genetic tools and in sequencing the human genome will accelerate the understanding of complex genetic diseases. However, phenotypic clinical data needs to be obtained and recorded to a similar degree of precision in order to match the wealth of molecular genetic data. To achieve this goal, large scale phenotypic databases of complex genetic diseases are under construction. LURIC (the LUwigshafen Risk and Cardiovascular Health Study) is such a project, aiming to identify new genetic and environmental risk factors or markers for cardiovascular disease in order to better understand the pathophysiology of complex genetic disease. It should also allow the determination of the prognostic role of new markers by studying functional genomics, (the association between a gene variant and phenotype), and pharmacogenomics (the influence of genetic variation on the response to therapeutic agents).

Cardiovascular Diseases↗
PubMed2001

Rationale and design of the LURIC study--a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease.

BACKGROUND AND AIM: Coronary artery disease (CAD), arterial hypertension and Type 2 diabetes mellitus are common polygenetic disorders which have a major impact on public health. Disease prevalence and progression to cardiovascular complications, such as myocardial infarction (MI), stroke or heart failure, are the product of environment and gene interaction. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study aims to provide a well-defined resource for the study of environmental and genetic risk factors, and their interactions, and the study of functional relationships between gene variation and biochemical phenotype (functional genomics) or response to medication (pharmacogenomics). Long-term follow-up on clinical events will allow us to study the prognostic importance of common genetic variants (polymorphisms) and plasma biomarkers. SETTING: Cardiology unit in tertiary care medical centre in south-west Germany. STUDY DESIGN: Prospective cohort study of individuals with and without cardiovascular disease at baseline. PATIENTS AND METHODS: LURIC is an ongoing prospective study of currently > 3300 individuals in whom the cardiovascular and metabolic phenotypes CAD, MI, dyslipidaemia, hypertension, metabolic syndrome and diabetes mellitus have been defined or ruled out using standardised methodologies in all study participants. Inclusion criteria for LURIC were: German ancestry (limitation of genetic heterogeneity) clinical stability (except for acute coronary syndromes [ACSs]) availability of a coronary angiogram (this inclusion criterium was waived for family members provided that they met all other inclusion and exclusion criteria) Exclusion criteria were: any acute illness other than ACSs any chronic disease where non-cardiac disease predominated a history of malignancy within the past five years. Exclusion criteria were pre-specified in order to minimise the impact of concomitant non-cardiovascular disease on intermediate biochemical phenotypes or on clinical prognosis (limitation of clinical heterogeneity). A standardised personal and family history questionnaire and an extensive laboratory work-up (including glucose tolerance testing in non-diabetics and objective assessment of smoking exposure by determination of cotinine plasma levels) was obtained from all individuals after informed consent. A total of 115 ml of fasting venous blood was sampled for the determination of a pre-specified wide range of intermediate biochemical phenotypes in serum, plasma or whole blood, for leukocyte DNA extraction and immortalisation of B-lymphocytes. Biochemical phenotypes measured included markers of endothelial dysfunction, inflammation, oxidative status, coagulation, lipid metabolism and flow cytometric surface receptor expression of lympho-, mono- and thrombocytes. In addition, multiple aliquots of blood samples were stored for future analyses. RESULTS: A total of 3500 LURIC baseline measurements were performed in 3316 individuals between July 1997 and January 2000. The baseline examination was repeated within a median of 35 days in 5% of study participants (n = 166, including a third examination in 18 after a median of 69 days) for pharmacogenomic assessment of lipid-lowering therapy and for quality control purposes. A five-year follow-up on major clinical events (death, any cardiovascular event including MI, stroke and revascularisation, malignancy and any hospitalisation) is ongoing. The clinical phenotypes prevalent at baseline in the cohort of 2309 men (70%) with a mean age of 62 +/- 11 years and 1007 women (30%), mean age 65 +/- 10 years, were angiographically-documented CAD in 2567 (79%), MI in 1368 (41%), dyslipidaemia in 2050 (62%) with hypercholesterolaemia > or = 240 mg/dl (27%), hypertriglyceridaemia > or = 150 mg/dl (44%) and HDL-cholesterol < or = 35 mg/dl (38%) in individuals not treated with lipid-lowering agents, systemic hypertension in 1921 (58%), metabolic syndrome in 1591 (48%), Type 2 diabetes in 1063 (32%) and obesity defined by body mass index > or = 30 kg/m2 in 770 (23%). Control patients in whom CAD had been ruled out angiographically were five years younger than those with CAD (59 +/- 12 and 64 +/- 10 years, respectively; p < 0.001), twice as often females (48% compared to 25% females in the CAD group, p < 0.001) and had significantly less cardiovascular risk factors than individuals with CAD. The prevalence of specific cardiovascular risk subsets in LURIC, such as the elderly (> or = 75 years), was 375 (11%), while 213 (6%) were young adults (< 45 years) and 904 (27%) were postmenopausal women (90% of all females). A low risk status (< or = 1 out of the four traditional risk factors: dyslipidaemia, smoking, hypertension and diabetes mellitus) was identified in 314 (9%) individuals of the entire cohort (5% in CAD and 26% in controls, p < 0.001) and 97 (3%) carried none of the four risk factors (1% in CAD and 9% in controls, p < 0.001). (ABSTRACT TRUNCATED)

Cardiovascular Diseases↗
PubMed2001

The significance of genetic polymorphisms in modulating the response to lipid-lowering drugs.

The response to lipid-lowering drugs is modified by a number of factors like age, gender, concomitant disease and genetic determinants. Even within homogenous groups of patients, individual responses vary greatly. Until now, no clinical or biochemical parameter exists which predicts whether a subject will respond well to a particular lipid-lowering drug or, in the extreme case, will develop adverse, life-threatening effects (e.g., myositis or rhabdomyolysis). The recent advances in the human genome project promises to have a great impact on our understanding of lipid and lipoprotein metabolism and of the individual response to lipid-lowering drugs. Monogenetic disorders of the lipid metabolism produce severe clinical phenotypes, such as Tangier disease, but have a minor role in the evaluation of cardiovascular risk in the general population. On the other hand, several polymorphisms in genes involved in lipoprotein metabolism (e.g., apolipoprotein E) are associated with the plasma levels of lipoproteins, explaining a substantial fraction of the variance of LDL or HDL concentrations. In combination, the knowledge of these polymorphisms, further variants yet to be discovered and variants within the genes involved in the metabolism of lipid-lowering drugs will in the future allow these drugs to be selected according to the patients needs and thus increase both efficacy and cost-effectiveness of lipid-lowering regimes.

Animals↗
PubMed2001

Cigarette smoking is independently associated with markers of endothelial dysfunction and hyperinsulinaemia in nondiabetic individuals with coronary artery disease.

BACKGROUND: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified. STUDY OBJECTIVES: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease. DESIGN: Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements. SETTING: Cardiology and cardiac surgery unit of a tertiary care referral centre. PATIENTS AND METHODS: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis. RESULTS: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001). CONCLUSIONS: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.

Biomarkers↗
PubMed2000

Genetic variation in coronary heart disease and myocardial infarction: methodological overview and clinical evidence.

The precise molecular mechanisrms that lead to coronary artery disease (CAD) and myocardial infarction (MI) are not understood, despite a wealth of knowledge on predisposing risk factors and pathomechanisms. CAD and MI are complex genetic diseases; neither the environment alone nor a single gene cause disease, but a mix of environmental and genetic factors lead to atherosclerosis of the coronary arteries and subsequent manifestation of clinical disease. The biological complexity of atherosclerotic disease results from unknown or unpredictable interactions of many genetic and environmental factors which, by themselves, have only been partially identified. According to current knowledge, genetic variations in causative or susceptihility genes form the basis of molecular mechanisms that, together with environmental impact, lead to CAD/MI and determine its clinical course. Linkage analysis, which follows 'disease' alleles in families, or genetic association in a population of unrelated individuals are tools used in the search for chromosomal loci and candidate genes that are involved in these complex diseases. Progress in sequencing and mapping of the human genorne and efforts to identify all of the expected one million single nucleotide polymorphisms (SNPs) expected to be present in mankind will allow new approaches such as genome-wide association studies. The contribution of the current state of knowledge on genetic variation in man towards the dissection of CAD/MI as complex traits is sobering. Raised expectations with regard to the power of molecular genetic studies as compared to the traditional pathophysiological experimental approaches, lack of precise clinical phenotyping, lack of functional characterisation of gene variants, and the vast number of yet undetected genes may provide some explanation. Except for certain polymorphisms in lipid genes (i.e., apolipoprotein E [apo E]) or rare genetic variations (i.e., LDL receptor), which have a causal effect on both the intermediate (LDL-cholesterol level in plasma) and the clinical phenotypes (CAD/MI), the role of most gene polymorphisms is controversial or unknown. Despite the enormous progress in sequencing the human genome and in molecular genetic and bioinformatic techniques during the past decade, the progress in mapping and identifying genes responsible for complex traits such as CAD/MI has been modest and presents a formidable challenge to medical research in the 21st century.

Coronary Disease↗
PubMed1999

Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease.

BACKGROUND: Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects. METHODS AND RESULTS: This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L; 1 allele, 15.7 +/- 5.1 nmol/L; 2 alleles, 17.3 +/- 4.7 nmol/L; P =.006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P =.001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents ( P <.05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5; 95% confidence intervals 1.1 to 2.1, P =.03, and 1.0 to 2.1, P =.05, respectively). CONCLUSIONS: The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.

Alleles↗
PubMed1998

Tumour necrosis factor beta alleles and hyperinsulinaemia in coronary artery disease.

BACKGROUND: Hyperinsulinaemia and dyslipoproteinaemia are markers and risk factors for coronary artery disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM). We investigated the influence of a tumour necrosis factor beta (TNF-beta) gene polymorphism on serum parameters related to these metabolic disorders in patients with CAD. METHODS: A total of 199 patients with CAD and 81 control subjects with angiographically normal coronary arteries were studied. A digestion of amplified DNA with NcoI revealed three fragment patterns: homozygosity for TNF-beta *1 or TNF-beta *2 and heterozygosity (TNF-beta *1/*2). RESULTS: Patients with CAD who had increased serum insulin or C-peptide (fasting and after glucose load) were predominantly heterozygous for TNF-beta (72% vs. 47%) and less frequently homozygous for TNF-beta *2 (22% vs. 43%, P = 0 x 0.03). CONCLUSION: This study demonstrates an association of TNF-beta alleles with the risk factor hyperinsulinaemia in CAD. Genomic variants of TNF-beta may therefore contribute to the complex susceptibility for the metabolic syndrome in patients with CAD.

Alleles↗
PubMed1998

Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting.

BACKGROUND: An alarming incidence (1% to 83%) of neuropsychological dysfunction has been reported after operations using cardiopulmonary bypass (CPB). The present clinical study re-evaluates these complications with current CPB technology in a strictly selected low-risk group of coronary artery bypass (CABG) patients. METHODS: 76 CABG patients, without history of stroke or internal carotid artery stenosis, were examined before, 5 days after, and 2 months after surgery. A neuropsychological test battery was employed according to the "Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac Surgery". Tests include the Block Design Test (problem-solving strategies, recognition and analysis of forms), the Trail Making Test (cognitive achievement at speed), and the Digit Span Test (short-term memory and memory of figures). RESULTS: Both postoperative test scores were not significantly decreased as compared to preoperative values. In contrast, neuron specific enolase (NSE) and S100 b protein, biochemical markers of cerebral injury, increased markedly during and immediately after surgery (NSE preop.: 7.07 +/- 2.40 ng/ml, 1 h postop.: 13.64 +/- 4.50 ng/ml, p < 0.001; S100 b preop.: 0.04 +/- 0.07 ng/ml, after crossclamp: 0.90 +/- 0.69 ng/ml, p < 0.001). One patient displayed postoperative transitional syndrome, another patient suffered from transitory paresis and hypesthesia of the left arm, which disappeared during hospital stay. CONCLUSIONS: Biochemical markers demonstrate significant postoperative cerebral injury during and immediately after CPB. However, CPB for CABG does not lead to marked impairment of neuropsychological scores, and clinically relevant neurological findings were observed in one patient only.

Aged↗
PubMed1998

Polymorphism of platelet membrane glycoprotein IIIa: human platelet antigen 1b (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in coronary artery disease.

Conflicting results of an association between the human platelet antigen 1b (HPA-1b or PlA2) allele and the risk of myocardial infarction and coronary artery disease have been reported. To assess the reason for this discrepancy, we determined the HPA-1 genotype in 298 men who had undergone coronary angiography, including 124 individuals with myocardial infarction, 83 individuals with coronary artery disease but no history of myocardial infarction, and 91 control patients. Among patients with acute or recent onset myocardial infarction (< 1 year), the prevalence of HPA-1b was higher than among patients with coronary artery disease but without myocardial infarction (33 percent vs. 14 percent, p = 0.016). In patients under 60 years of age this difference was even more pronounced (45 percent vs. 15 percent, p = 0.003). Unlike conventional risk factors HPA-1b does not represent a risk factor for coronary artery disease itself but appears to be associated with increased platelet thrombogenicity.

Adult↗
PubMed1996

Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease.

BACKGROUND: Previous research has shown that the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is a major determinant of plasma ACE activity. It has been suggested that persons with the DD genotype (those who express, on average, the highest levels of circulating ACE) have an increased risk for myocardial infarction and coronary artery disease, particularly if they are otherwise at low risk. Subsequent studies, however, have not confirmed that ACE I/D gene polymorphism is a risk factor for coronary artery disease and myocardial infarction. OBJECTIVE: To investigate the association between the I/D polymorphism of the ACE gene and the risk for coronary artery disease and myocardial infarction in patients in whom coronary artery disease status was documented by angiography. DESIGN: Cross-sectional study. SETTING: University medical center. PATIENTS: 209 male case-patients with coronary artery disease and 92 male controls without coronary artery disease, as documented by coronary angiography. MEASUREMENTS: Assessment of the cardiac risk profile by questionnaire; classification of patients by the degree of coronary artery stenosis; levels of lipoproteins, apolipoproteins, and fibrinogen; and ACE I/D gene polymorphism assessed by polymerase chain reaction amplification. RESULTS: Plasma ACE activity was significantly associated with ACE I/D gene polymorphism. The ACE genotype was not associated with the presence of coronary artery disease or myocardial infarction. If a recessive effect of the D allele was assumed (DD compared with DI and II), the relative risk was 1.00 (95% CI, 0.76 to 1.30) for coronary artery disease and 1.03 (CI, 0.77 to 1.38) for myocardial infarction. Results of analyses were also negative when a dominant effect of the D allele was assumed and when low-risk subgroups were examined. The established risk factors age and apolipoprotein B level emerged as the most important risk predictors in multivariate analyses, followed by diastolic blood pressure and fasting glucose levels. CONCLUSIONS: In an angiographically defined study sample, ACE I/D gene polymorphism was not associated with an increased risk for coronary artery disease or myocardial infarction, despite its effects on plasma ACE activity.

Aged↗
PubMed1996

Experimental application of controlled limb reperfusion after incomplete ischaemia.

Severe local and systemic complications may occur after revascularization of extremities exposed to prolonged complete or incomplete ischaemia. These complications may be reduced by controlling the reperfusate and the circumstances of the reperfusion period. Ten adult German domestic pigs were exposed to 6 h of incomplete limb ischaemia by occlusion of the left iliac artery. To simulate the clinical situation of embolectomy, the occlusive snares were released after the ischaemic period in five pigs and normal blood flow developed with systemic pressure (uncontrolled reperfusion). In the other five pigs, a controlled reperfusate was delivered at controlled pressure before establishing normal blood reperfusion (controlled reperfusion). At the end of the observation period (90 min after start of reperfusion), the group with controlled reperfusion had a lower mean(s.e.m.) tissue water content (81.8(0.7) versus 84.3(0.7) per cent, P < 0.05, a greater increase in tissue adenosine 5'-triphosphate compared with values at the end of ischaemia (6.2(1.5) versus -2.5(1.8) mumol per g protein, P < 0.03), a higher tissue pH (7.2(0.1) versus 6.8(0.1), P < 0.03), a smaller temperature decrease (0.3(0.2) versus 1.2(0.3) degrees C, P < 0.05), lower concentrations of creatine kinase (355.0(87.5) versus 624.4(73.4) units/l, P < 0.05) and lactate dehydrogenase (LDH) (369.5(42.5) versus 538.4(39.2 units/l, P < 0.03) in the femoral vein blood and lower LDH concentrations (356.5(48.9) versus 546.0(37.8 units/l, P < 0.03) in central venous blood. These data indicate that severe local and systemic damage occurs with uncontrolled (normal blood) reperfusion even after incomplete limb ischaemia, and that these changes can be reduced by delivering a controlled reperfusate under controlled conditions.

Adenosine Triphosphate↗
PubMed1996

Hormonal modifications in patients admitted to an internal intensive care unit for acute hypoxaemic respiratory failure.

To clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H). In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H. In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant.

Acute Disease↗