PubMed Health⌕ Search

Biomedical subjects

A A Driedger

Publications and source records attributed to A A Driedger.

At least 55 records · Page 3Linked to original sources

Hypophosphatemia and respiratory failure: prolonged abnormal energy metabolism demonstrated by nuclear magnetic resonance spectroscopy.

Hypophosphatemia has been shown to cause acute respiratory failure. The mechanism is believed to be due to decreased high-energy substrate availability at the cellular level leading to respiratory muscle dysfunction. However, direct measurement of these substrates has not been previously studied. A patient with hypophosphatemic respiratory failure is described in whom phosphocreatine and pH were continuously monitored using nuclear magnetic resonance spectroscopy. This revealed a defect in muscle metabolism that required several weeks to recover despite prompt correction of the serum phosphate level.

Acute Disease↗

Hemodynamic adaptation to acute myocardial contusion complicating blunt chest injury.

The immediate hemodynamic sequelae of blunt chest injury complicated by acute myocardial contusion were examined in multiply traumatized patients. Focal defects of ventricular wall motion defined by gated cardiac scintigraphy identified acute myocardial contusion in 28 of 43 patients, involving the right ventricle alone in 18 (group 1A), the left ventricle in 4 (group 1B) and both ventricles in 6 (group 1C). Qualitatively normal ventricular wall motion was found in the 15 patients (group 2). Although there was no difference between groups 1A and 2 in mean systemic oxygen transport (620 +/- 189 vs 627 +/- 105 ml/min/m2), left ventricular ejection fraction (52 +/- 14% vs 60 +/- 9%) or calculated left ventricular end-diastolic and end-diastolic and end-systolic volumes, mean right ventricular (RV) ejection fraction was significantly lower in group 1A (29 +/- 9%) than in group 2 (47 +/- 7%, p less than 0.01). Concomitantly, evidence of RV systolic dysfunction was ml/m2) but not in group 2 (RV end-systolic volume, 50 +/- 21 ml/m2, p less than 0.05). RV stroke work was similar between the groups, and RV pump function was identical by virtue of a larger RV preload in group 1A (RV end-diastolic volume 143 +/- 63 ml/m2) than in group 2 (RV end-diastolic volume 93 +/- 26 ml/m2, p less than 0.05). Thus, use of the RV Frank-Starling mechanism in patients with traumatic RV contusion maintains RV pump function at a level similar to that in traumatized patients without acute myocardial contusion.

Adaptation, Physiological↗

Preparation and evaluation of radioiodinated (iodophenyl)cholines and their morpholinium and piperidinium analogues as myocardial perfusion imaging agents.

A series of nine radioiodinated quaternary ammonium salts related to phenylcholine were synthesized, characterized, and radiolabeled by exchange. These compounds were evaluated as myocardial perfusion imaging agents in mice, pigs, and humans. Mice biodistribution studies showed that five of the nine compounds were taken up in the heart to the same extent as 201Tl+ at 5 min. At 60 min myocardial retention was significantly better than 201Tl+ for six of the compounds. Several of the compounds showed more favorable heart/blood and heart/liver ratios when compared to 201Tl+. Evaluation of three of the more promising compounds in pigs and humans however revealed no selective myocardial uptake.

Animals↗

Increased activity on immediate phase of bone imaging does not always indicate increased blood volume.

The immediate Tc-99m MDP image of a neoplastic right wrist mass in a 10-year-old boy demonstrated intense focal accumulation that suggested a very vascular tumor, but delayed images showed only slightly increased activity in the mass. A Tc-99m labeled RBC study was performed to permit whole-body blood pool imaging for other vascular lesions, and it did not demonstrate an increased blood volume in the mass. Biopsy showed the tumor to be a Ewing's sarcoma, probably of soft tissue origin. The sarcoma was not very vascular. The intense immediate accumulation of Tc-99m MDP in this case may be attributed to increased microvascular permeability.

Biopsy↗

Right and left ventricular performance in acute hypoxemic respiratory failure.

We examined biventricular performance on two occasions in 28 patients with acute hypoxemic respiratory failure (ARF), using a combination of invasively determined pressures and flows as well as radionuclide scintigraphy to measure the right and left ventricular ejection fractions (RVEF and LVEF, respectively). From the EF and concurrently measured thermodilution stroke volumes, we calculated right and left ventricular end-diastolic and end-systolic volume indices (EDVI and ESVI, respectively). Regression analysis demonstrated that changes (delta) in global right ventricular function (RVEF) were inversely correlated with concurrent changes in the mean pulmonary arterial pressure (MPAP): delta RVEF = 0.015-0.015 delta MPAP (r2 = 0.60; p less than .005), while an increase in right ventricular preload (RVEDVI) was positively correlated with changes in MPAP: delta RVEDVI = 2.68 +/- 6.27 delta MPAP (r2 = 0.46; p less than .005). Global left ventricular function (LVEF) was related to changes in systemic pressures as well as to right-sided events: delta LVEF = -0.01-0.0015(delta RVESVI) + 0.001(delta BP systolic)-0.42(CVP/RVEDVI) (r2 = 0.35; p less than .01). These data confirm the significant influence of right ventricular afterload on RVEF in ARF patients and an apparent interrelationship between altered right ventricular systolic function and global left ventricular performance.

Acute Disease↗

Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome. Qualitative and quantitative assessment of pulmonary neutrophil kinetics in humans with in vivo 111indium neutrophil scintigraphy.

In the absence of direct toxins, the majority of evidence from animal models suggests that neutrophils (PMN) are necessary for the full expression of the abnormal pulmonary permeability accompanying acute microvascular lung injury. We therefore studied the role of the PMN in the human correlate of this disease, the adult respiratory distress syndrome (ARDS), by assessing the pulmonary retention of infused autologous 111Indium-labeled PMN (PMN-In). We evaluated 79 patients, prospectively categorized as: "active" ARDS (Aa; n = 30), "active" ARDS and concurrent corticosteroid therapy (As; n = 11), "resolving" ARDS (Ar; n = 13), sepsis without pulmonary edema (S; n = 7), and cardiac pulmonary edema (C; n = 18). This clinical separation was confirmed by retrospective analysis of associated measures of hemodynamic and respiratory dysfunction. We found that both analog scintigrams (positive/negative for diffuse pulmonary PMN-In sequestration) and computer-assisted quantitative analysis in 46 patients (T 1/2 of first hour demargination and percentage of peak activity/pixel/second remaining at 17 to 20 h) showed a significant rank order decrease in the pulmonary retention of labeled PMN-In through the Groups Aa----As----S----Ar----C. Our findings recognized aspects of in vivo PMN-In behavior that implied pathophysiologic differences between groups of critically ill patients in either the PMN themselves or in PMN-pulmonary endothelial interaction. This demonstrates the possibility of abnormal in vivo PMN-endothelial interaction in ARDS by virtue of the greater pulmonary localization of PMN in active ARDS versus resolving disease, septic non-ARDS states, and cardiac pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Lack of significant long-term sequelae following traumatic myocardial contusion.

We assessed the possibility of long-term functional cardiac sequelae in patients who had sustained a traumatic myocardial contusion (group 1) by comparing this group with a cohort group of patients with similar traumatic injuries but exclusive of the cardiac component (group 2). More than one year following injury, patients in group 1 were qualitatively indistinguishable from patients in group 2 according to the New York Heart Association classification. Both the left and the right ventricular ejection fractions, less in group 1 than in group 2 immediately following trauma, were similar between groups during follow-up study at rest. During exercise to maximal work load at follow-up, changes in the mean right and left ventricular ejection fractions were also similar between the two patient groups. We therefore concluded that traumatic myocardial contusion to the left and/or right ventricle almost always resolves without significant functional sequelae within one year of injury.

Adolescent↗

Pulmonary microvascular fluid flux in a large animal model of sepsis: evidence for increased pulmonary endothelial permeability accompanying surgically induced peritonitis in sheep.

To characterize some of the remote effects of systemic sepsis on the lung, we evaluated changes in pulmonary microvascular fluid flux before and during sepsis secondary to a peritoneal focus of inflammation in sheep. We induced peritonitis by cecal ligation, perforation, and devascularization. During a subsequent 72-hour study period, both the mean blood pressure and the pulmonary capillary wedge pressure were unchanged, while the cardiac index increased slightly. The PaO2 fell by 48 hours (98 +/- 8 to 84 +/- 10 mm Hg; p less than 0.05) (mean +/- SD) and subsequently remained low throughout the experiment. Simultaneously, pulmonary lymph flow increased by 24 hours (11.5 +/- 4.9 to 26.7 +/- 13 ml/hr; p less than 0.05) and remained elevated throughout the experiment while [L/P] total protein ratios remained unchanged at 24 hours (baseline: 0.59 +/- 0.15 at 24 hours: 0.65 +/- 0.16). Morphologic examination of the lung showed that this model of peritonitis was characterized by neutrophil emigration into the pulmonary interstitium by 24 hours and interstitial edema by 48 hours. Therefore this model of bacterial peritonitis in sheep demonstrates that one of the remote effects of surgically induced systemic sepsis is an increase in permeability of the pulmonary microvascular membrane.

Animals↗

The immediate effects of isosorbide dinitrate on right ventricular function in patients with acute hypoxemic respiratory failure. A combined invasive and radionuclide study.

We administered 20 mg of isosorbide dinitrate sublingually to 16 patients with acute hypoxemic respiratory failure (ARF) complicated by pulmonary artery hypertension (PAH) and evaluated its effects 20 to 30 min later using a combination of invasively measured pressures and flows and ECG-gated cardiac scintigraphy. We measured the right and left ventricular ejection fractions and a simultaneous thermodilution stroke volume index; we then calculated respective end-diastolic (EDVI) and end-systolic (ESVI) volume indexes. An initially depressed mean right ventricular ejection fraction (RVEF) increased modestly after the administration of isosorbide dinitrate (35 +/- 10 to 41 +/- 10%; p less than 0.02), whereas both the mean right ventricular end-diastolic (-27 +/- 50 ml/M2; p less than 0.04) and end-systolic (-27 +/- 44 ml/M2; p less than 0.03) volume indexes fell. The RVEF increased in 11 of 16 patients: within this subgroup, a decrease in the RVEDVI and RVESVI was associated with a decrease in both cardiac index (delta 0.3 L/min/M2) and LVEDVI (delta -15 +/- 21 ml/M2; p less than 0.01); hence, O2 delivery also fell (delta -36 +/- 56 ml/min/M2; p less than 0.05). In some patients with ARF complicated by PAH, sublingually administered nitrates may improve right ventricular systolic function when globally depressed. However, left ventricular "pump" function appears to be depressed when a concurrent depression in right ventricular "pump" function ensues.

Acute Disease↗

Assisted ventilation in patients with preexisting cardiopulmonary disease. The effect on systemic oxygen consumption, oxygen transport, and tissue perfusion variables.

We have evaluated systemic oxygen consumption (VO2), systemic oxygen transport, and tissue perfusion variables in 30 patients with preexisting cardiac and underlying pulmonary disease during continuous positive-pressure ventilation and positive end-expiratory pressure [PEEP], during intermittent mandatory ventilation (IMV and PEEP), and during spontaneous ventilation (continuous positive airway pressure [CPAP]), with end-expiratory pressure held constant during all ventilatory modes. Using radionuclide angiography together with invasive determinations of pressure and flow, we also measured left and right ventricular ejection fractions and calculated the end-systolic (ESVI) and end-diastolic (EDVI) volume indices of both ventricles. We found that oxygen transport was significantly greater during CPAP (583 +/- 172 ml/min/M2)(mean +/- SD) than during either IMV and PEEP (543 +/- 151 ml/min/sq; p less than 0.01) or CPPV and PEEP (526 +/- 159 ml/min/M2; p less than 0.01); however, we found no significant change in systemic VO2 with conversion from CPPV and PEEP to CPAP. The increase in oxygen transport was related to a greater cardiac index and, more specifically, to a higher heart rate during CPAP (CPAP, 106 +/- 16 beats per minute; CPPV and PEEP, 97 +/- 14 beats per minute) (p less than 0.01). Enhanced oxygen transport during CPAP was also associated with an increase in mixed venous oxygenation and a decrease in arterial lactate. Although neither the mean left ventricular EDVI nor ESVI changed from CPPV and PEEP to CPAP, the mean pulmonary capillary wedge pressure increased (CPPV and PEEP, 12 +/- 5 mm Hg; CPAP, 14 +/- 7 mm Hg) (p less than 0.01), suggesting the possibility of a decrease in left ventricular compliance with the spontaneous ventilatory mode. This study suggests that in the absence of ventilatory failure, spontaneous ventilation provides for better systemic oxygen transport and overall tissue perfusion than either controlled ventilation or IMV; however, this benefit of enhanced oxygen delivery with spontaneous ventilation may potentially be offset by a decrease in left ventricular compliance.

Aged↗

Gallium67 scintigraphy in the diagnosis of acute renal disease.

67Ga scintigraphy was performed in 44 patients with various biopsy proven forms of renal disease and in a further 64 patients, some with clinically diagnosed renal disease and some with non-renal disorders. Renal uptake of gallium at 48 hours was graded by two blinded observers and by tissue ratios determined by computer. All 11 patients with biopsy proven acute drug-induced interstitial nephritis demonstrated intense, diffuse, bilateral renal 67Ga uptake, a phenomenon observed in only five of the other 30 patients with biopsy proven renal disease and in four of the 64 patients with clinical diagnoses only. No patient with acute tubular necrosis demonstrated significant renal gallium uptake. It is suggested that 67Ga scintigraphy is an excellent screening test for the presence of acute interstitial nephritis and helps to identify which patients with unexplained acute renal failure require renal biopsy.

Acute Disease↗

Noninvasive clinical investigation of the cardiovascular system in the critically ill.

An understanding of fundamental principles of various modes of noninvasive cardiovascular monitoring is important in the investigation and management of acute cardiac illnesses found in the critically ill. The clinical application of electrocardiography, radiology, echocardiography, and nuclear medicine will be discussed as it applies to investigation and management of the cardiovascular system in these patients.

Cardiovascular System↗

The synergistic influence of the intravascular starling forces on pulmonary microvascular solute flux in human ARDS.

To assess the importance of the intravascular Starling forces on the pulmonary microvascular flux of solutes in ARDS, the clearance from blood to pulmonary edema fluid of a small-molecular-weight hydrophilic radiotracer, indium-111-DTPA, and a large-molecular-weight radiotracer, iodine-125-HSA, in patients with noncardiac pulmonary edema was measured. Since permeability changes of the pulmonary microvessels in ARDS are likely not homogeneous, the severity of the permeability lesion according to the magnitude of I-HSA flux was predefined. A significant positive correlation between the clearance of In-DTPA and the Pmv-pi mv gradient was found both in patients with a "moderate" (R2 = 0.46, P less than 0.01) and "severe" (R2 = 0.45 P less than 0.01) increase in microvascular permeability. The clearance of I-HSA from blood to edema fluid was also positively correlated with the Pmv and the Pmv-pi gradient. Therefore, even though ARDS is primarily characterized by a spectrum of change in permeability within the pulmonary microvasculature, the flux of both small- and large-molecular-weight solutes remains synergistically modulated by the measurable intravascular Starling forces.

Cell Membrane Permeability↗

The effect of an infusion of zymosan-activated plasma on hemodynamic and pulmonary function in sheep.

To assess the integrated cardiopulmonary response to acute microvascular lung injury, we infused zymosan-activated plasma (ZAP) into mature, awake sheep. ZAP infusion resulted in an immediate increase in the mean pulmonary artery pressure (PAP) from 17.5 +/- 4.5 mm Hg to a maximum of 33.0 +/- 5.4 mm Hg by 5 min (p less than 0.01) of a 90-min infusion. The pulmonary artery hypertension (PAH) was sustained throughout ZAP infusion, and for up to 30 min after infusion was completed (p less than 0.05). Lung lymph flow increased immediately, but lymph to plasma total protein ([L/P]) ratios remained unchanged, suggesting increased pulmonary microvascular permeability. The PaO2 fell to a minimum by 5 min (106.9 +/- 17 to 88.3 +/- 14 mm Hg; p less than 0.01), but recovered toward preinfusion values in the final 60 minutes of ZAP infusion. The cardiac index (CI) and stroke volume index (SVI) also fell significantly for 15 minutes (p less than 0.01), and then recovered to levels not different from baseline by 30 min. In parallel with all of these changes, the polymorphonuclear leukocyte count (PMN) in arterial blood fell immediately [baseline to 5 min, delta 4.9 +/- 2.5 (X 10(3))/mm3; (p less than 0.01)] due to sequestration within the pulmonary microvasculature, since a baseline PMNs were being released from the lung, -6.0 +/- 19%, while by 15 min the PMNs were being sequestered, +58.4 +/- 31% (p less than 0.01). Therefore, ZAP infusion reproduced the clinical picture of acute microvascular lung injury in humans, specifically acute PAH and increased pulmonary microvascular permeability. These two changes were due to a cascade of events associated with the pulmonary microvascular trapping of PMNs.

Animals↗

Frequency of myocardial injury after blunt chest trauma as evaluated by radionuclide angiography.

Seventy-seven patients who had sustained multisystem trauma, including severe blunt chest injury, were prospectively evaluated to assess the frequency of associated traumatic myocardial injury. Traumatic injury to either the right or left ventricle was defined by the presence of discrete abnormalities of wall motion on electrocardiographically gated cardiac scintigraphy in patients without a clinical history of heart disease. Forty-two patients (55%) (Group 1) had focal abnormalities of wall motion; 27 involved the right ventricle, 7 the left ventricle, 7 were biventricular, and 1 involved only the septum. Both the right and left ventricular ejection fractions were significantly (p less than 0.01) lower (31 +/- 11% and 47 +/- 14%, respectively) than those in the 35 traumatized patients without wall motion abnormalities on scintigraphy (Group 2) (49 +/- 8% and 58 +/- 11%, respectively). Repeat scintigraphic examination in 32 Group 1 patients at a time remote from initial injury showed improvement or resolution of previously defined focal wall motion abnormalities in 27 of 32 patients (84%). The electrocardiogram and serum enzyme tests were insensitive indexes of traumatic myocardial injury when defined by the scintigraphic abnormalities. Thus, severe blunt chest trauma results in a higher frequency of traumatic myocardial injury than heretofore recognized, and frequently involves the anteriorly situated right ventricle.

Adolescent↗

Concepts in the pharmacologic and nonpharmacologic support of cardiovascular function in critically ill surgical patients.

The critically ill surgical patient requires close clinical, biochemical, and hemodynamic monitoring to define the right timing as well as the proper type of therapeutic intervention. Although many factors are available for monitoring, O2 delivery and extraction are two of the most important, since the enhanced metabolic demands of the stressed patient dictate a need to maintain greater than normal values to ensure survival. In other situations, primary therapy of the blood pressure, the PCWP, or other indices may take temporary precedence in the choice of therapeutic agents. Regardless of the means used to optimize O2 delivery, scrutiny of the consequences of therapy is equally important. Above all, any therapeutic intervention does not negate the need to treat the primary underlying process expeditiously.

Blood Circulation↗

Clinical correlates of the spectrum of lung microvascular injury in human noncardiac edema.

We measured the clearance from blood to pulmonary edema fluid of a small molecular weight hydrophilic radiotracer, Indium-111-DTPA (In-DTPA) and a larger molecular weight radiotracer, Iodine-125-HSA (I-HSA), in patients with pulmonary edema on either a cardiac or noncardiac (permeability) basis. In previous investigations, we had noted an apparent relationship between the magnitude of clearance of I-HSA across the alveolocapillary membrane and the severity of noncardiac pulmonary edema. In this study, we were able to distinguish at least 2 distinct groups of patients with noncardiac pulmonary edema. Patients with the greatest damage to the alveolo-capillary exchanging membrane, defined by the flux of I-HSA from blood to edema fluid, were significantly differentiated from those with a lesser microvascular injury on the basis of higher mean heart rate (HR), temperature, cardiac index (CI), pulmonary artery pressures, right ventricular stroke work index (RVSWI), and a lower mean total white blood cell count (WBC), among others. Therefore, noncardiac pulmonary edema is characterized by a spectrum of permeability injury to the pulmonary microvasculature which seems to parallel other measurable indices of the severity of the systemic response to the illness.

Cell Membrane Permeability↗

Right ventricular function in acute disease states: pathophysiologic considerations.

In critically ill patients, alterations in pulmonary vasomotor tone profoundly influence right ventricular (RV) function. An increase in end-diastolic volume (EDV) follows elevations in the RV afterload, this increase in preload probably subserving the increased RV stroke work (SW) required to ensure unchanged RV pump function. The maintenance of a normal left ventricular (LV) preload is essential in the cardiovascular adaptation to an acute illness. With volume overload of the RV consequent upon pulmonary artery hypertension (PAH), leftward septal shift occurs and reduces LV diastolic compliance. With extremely high levels of RV loading conditions, a depression in RV contractility and reduced RV pump function are eventually seen, both of which then become partially responsible for LV pump failure. Hence, abnormalities in RV function will have a marked clinical influence on the circulatory response seen in critically ill patients. Future investigation should be directed toward the effects of augmenting or improving RV function with pharmacologic agents in this patient population.

Blood Pressure↗