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T D Rohde

Publications and source records attributed to T D Rohde.

At least 19 recordsLinked to original sources

Plasma cholesterol: an influencing factor in red blood cell oxygen release and cellular oxygen availability.

BACKGROUND: A fairly immediate reduction in angina pectoris symptoms after cholesterol lowering has been described. Our previous findings in rabbits and in a four-patient human pilot study indicated the existence of an RBC membrane barrier to oxygen (O2) transport in the presence of hypercholesterolemia. Our current objective was to determine whether, and to what extent, the plasma cholesterol concentration is an influencing factor in RBC O2 release and cellular O2 availability. STUDY DESIGN: In an unique O2 diffusion analysis system, blood samples from 100 patients referred for lipid modification were analyzed. After 1 to 2 minutes of mixing in our diffusion analysis system, the next 1 to 2 minutes of circulation is comparable with 1 to 2 seconds of myocardial capillary flow. RBC O2 diffusion was defined by the depletion rate of total O2 content in blood from full O2 saturation (98%) to desaturation (approximately 60%). Relative tissue O2 availability was defined as the percentage decrease in O2 availability between the high-cholesterol group and the low-cholesterol group. RESULTS: The 100 patients were divided almost equally into two groups on the basis of plasma cholesterol ranges of 175 to 229 mg/dL (n=49) and 230 to 299 mg/dL (n = 51). The mean cholesterol concentrations and percentage increases in the high-cholesterol group over the low-cholesterol group were: for plasma, 206 +/- 0.3 and 256 +/- 0.4 mg/dL, 24.3% (p < 0.001); for RBCs, 93 +/- 0.2 and 106 +/- 0.2mg/dL, 14.0% (p < 0.001); and for RBC membranes, 41 +/- 0.1 and 54 +/- 0.2mg/dL, 31.7% (p < 0.001). The blood O2 diffusion curves were distinctly different between the high- and the low-cholesterol groups (p < 0.05). Blood O2 diffusion, defined by the blood O2 diffusion curves, was inversely proportional to the plasma, RBC, and RBC-membrane cholesterol concentrations. The relative tissue O2 availability, after a circulation period of more than 3 minutes in the diffusion system, showed a decrease of 17.5% (p < 0.05) between the plasma cholesterol groups. In comparing the two plasma cholesterol concentration extremes of less than 200mg/dL (n= 14) and greater than 275 mg/dL (n= 11) after a circulation period of more than 3 minutes in the diffusion system, we found a decrease in relative tissue O2 availability of 35.8% (p < 0.05). CONCLUSIONS: The plasma cholesterol concentration may be an influencing factor in RBC-membrane cholesterol content, which, in turn, may regulate RBC-membrane O2 transport, RBC O2 release, and cellular O2 availability. The implications of this work include the addition of angina pectoris control to the indications for appropriate lipid modification and the development of an in vitro blood stress test to replace patient cardiac stress testing.

Cholesterol↗

Effect of plasma cholesterol on red blood cell oxygen transport.

1. Oxygen (O2) transfer from the blood to tissues is a function of the red blood cell (RBC) O2 saturation (SO2), the plasma O2 content being negligible. Under conditions of increased tissue O2 demand, the SO2 of arterial blood does not change appreciably (97%); however, the SO2 of mixed venous blood, equal to that of the perfused tissues, can go as low as 20%. 2. Tissue O2 availability is limited by the exposure time to a RBC, which decreases under conditions of maximum stress (< 1 s). If the O2 unloading time was to increase significantly, because of a decrease in the RBC diffusion constant or an increase in the RBC membrane thickness, the RBC O2 unloading time would exceed tissue (e.g. cardiac) transit time and O2 transfer would be impaired. 3. Cholesterol constitutes the non-polar, hydrophobic lipid of the enveloping layer of the RBC membrane. As the cholesterol content of the RBC increases, the fluidity of the membrane decreases and the lipid shell stiffens. 4. Early studies demonstrated that high blood cholesterol concentrations were associated with reduced blood O2 transport; in essence, the haemoglobin dissociation curve was shifted to the left. 5. Current investigations have shown that the cholesterol RBC membrane barrier to O2 diffusion delayed O2 entry into the RBC during saturation and delayed O2 release from the RBC during desaturation. In an analysis of 93 patients divided by their cholesterol concentration into five groups, the percentage change in blood O2 diffusion was inversely proportional to the cholesterol concentration. 6. The RBC membrane cholesterol is in equilibrium with the plasma cholesterol concentration. It stands to reason that as the plasma cholesterol increases, the RBC membrane becomes impaired and O2 transport is reduced. 7. The implications of this new perspective on O2 transport include the ability to increase tissue oxygenation by lowering plasma cholesterol.

Animals↗

Decreased blood oxygen diffusion in hypercholesterolemia.

BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values. RESULTS: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.

Animals↗

A new peritoneovenous shunt.

For today's most common peritoneovenous shunt catheters, the high incidence of complications (disseminated intravascular coagulation [DIC], pulmonary problems, clotting of the intravascular end, and shunt kinking) results in limited use. We have designed a new peritoneovenous shunt catheter in which we improved mechanical biocompatibility with respect to both the peritoneum and the vasculature. The device consists of: a multimicroorifice ascites filter in a double-chambered collecting device, a tubular compression pump with an intratubular check-valve, and a check-valve catheter at the intravascular end for positive exclusion of blood by reflux or back diffusion. This configuration filters the proteinaceous material from the ascites fluid, transports the filtrate into the blood stream, maintains patency, act to prevent DIC by inhibiting the creation and transport of microthrombi into the cardiovascular system, and eliminates clot formation at the intravascular end.

Aged↗

Implantable infusion pump management of insulin resistant diabetes mellitus.

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare and brittle form of Type I diabetes, found predominantly in young females and characterized by inadequate glycemic response to subcutaneous or intramuscular insulin administration. DRIASM leads to frequent ketoacidosis and obligatory hospitalization for administration of intravenous insulin. The use of a totally implantable infusion pump effected dramatic improvement in the treatment of five patients with this difficult form of diabetes. Frequency of clinical ketoacidosis was reduced from 37 episodes per year to 0.4 episodes per year (99%), and average in-hospital days per month were reduced from 20.8 days to 2.2 days (89%) with a mean follow-up period of 14.4 months. Cost savings were approximately +10,000 per patient month. Quality of life was greatly improved for these individuals.

Adolescent↗

Reduction of plasma cholesterol and LDL-cholesterol by continuous intravenous insulin infusion.

We studied lipid profiles in 10 patients with insulin-requiring type II diabetes. Patients began the study under conventional subcutaneous insulin injection therapy. Treatment was then optimized on subcutaneous therapy and finally converted to continuous intravenous therapy from a single flow rate implantable pump. Pump management proved reliable and safe. Implantable pump therapy showed a statistically significant reduction in the average plasma cholesterol level from 205.7 to 184.7 mg/dl. The mean low-density lipoproteins (LDL)-cholesterol level decreased from 114.6 to 108.1 mg/dl, the high-density lipoproteins (HDL)-cholesterol average changed from 50.6 to 51.0 mg/dl, and the HDL/LDL ratio increased from 0.478 to 0.500. Glycemic control did not improve on single-rate intravenous therapy compared with intensive conventional subcutaneous injection during the short observation period. The authors conclude that additional studies should be performed to confirm the improvement in the lipid profile on intravenous pump therapy.

Adult↗

Failure to find amyloidosis in dogs treated with long-term intravenous insulin delivered by a totally implantable pump.

We examined tissues of seven non-diabetic mongrel dogs and four diabetic beagle dogs treated with constant insulin infusion via totally implantable pumps for from 210 to 880 days. Kidney and skeletal muscle tissue from all dogs were stained with Congo Red and thioflavin-T and appropriately examined. Kidney tissues from the beagle dogs were examined by electron microscopy. No amyloid deposits were found in any of these tissues. Thus, we cannot confirm an earlier report of amyloid occurring in dogs given long-term intravenous insulin. It is concluded that amyloidosis is not a necessary complication of long-term intravenous insulin infusion in dogs.

Amyloidosis↗

The use of an implantable insulin pump in the treatment of type II diabetes.

We treated five patients with Type II diabetes by means of a subcutaneously implanted intravenous insulin pump and compared their metabolic response with that observed during conventional insulin therapy. The use of the pump improved control of glycemia, as manifested by reductions in mean plasma glucose (from 188 +/- 46 to 106 +/- 12 mg per deciliter [mean +/- S.D.]), fasting glucose (from 187 +/- 42 to 80 +/- 13 mg per deciliter), and postprandial glucose (from 287 +/- 74 to 182 +/- 29 mg per deciliter), together with a diminution of glycemic excursion and normalization of glycosylated hemoglobin A1 (from 12.1 +/- 2 to 8.0 +/- 1 per cent). At the end of the study the pumps had been in place for a mean of 7.0 months (range, 5.5 to 9.7 months) without mishap and with good patient acceptance. Our data suggest that improved blood glucose control can be achieved by means of a permanently implanted continuous insulin-infusion device in ambulatory patients with Type II diabetes who require insulin, and that the need for daily insulin injections can thereby be eliminated.

Adult↗

Diabetic nephropathy in the uninephrectomized dog: microscopic lesions after one year.

Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with control by insulin injections permitting elevated fasting and postprandial serum glucose values and substantial glycosuria; the other with better control and with near-normal serum glucose levels and less glycosuria. By 1 year of diabetes both diabetic groups had renal lesions different from the uninephrectomized control animals but differing only slightly from one another. With light microscopy, diabetic dogs had increased mesangial thickening. With electron microscopic morphometry, glomeruli of diabetic subjects demonstrated increased fractional volumes of the total mesangium and of its cellular and matrix components and increased width of the GBM. These quantitative measures of diabetic nephropathy in the dog within 1 year of onset of the disease describe a model potentially useful in evaluating the efficacy of improved diabetic control in preventing or ameliorating diabetic nephropathy.

Animals↗