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Biomedical subjects

J Zhuang

Publications and source records attributed to J Zhuang.

At least 73 records · Page 4Linked to original sources
PubMed1994

The effect of hypertonic resuscitation on pial arteriolar tone after brain injury and shock.

Acute brain injury followed by hemorrhagic shock (HEM) causes prohibitive mortality in trauma patients because these combined events lead to low cerebral blood flow (CBF) and cerebral oxygen delivery (co2del). Proper treatment therefore requires rapid correction of cerebral perfusion deficits. Previous studies have shown that hypertonic crystalloid resuscitation significantly improves CBF and co2del in a model of brain injury and HEM when compared to lactated Ringer's (LR) solution. The mechanism or mechanisms for this advantage, however, are not well understood. We hypothesized that hypertonic fluid resuscitation would reduce pial arteriolar tone after brain injury and HEM resulting in an increase in CBF when compared to LR resuscitation. We measured cerebral and systemic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock over a 5-hour period. Swine were randomized to receive either hypertonic sodium lactate (HSL) or LR fluid resuscitation. The HSL resuscitation produced a significant and sustained elevation in cerebral perfusion pressure and pial arteriole diameter (p < 0.05), and a sustained elevation in CBF after brain injury and HEM when compared with LR. These data suggest that hypertonic fluid resuscitation following brain injury and HEM improves CBF, at least in part, by causing vasodilation of cerebral resistance vessels.

Animals↗
PubMed1994

[Chromosome 15 satellite enlargement and hereditary deafness].

The clinical and cytologic examinations in 6 deaf patients from 2 genealogical trees with chromosomal 15 satellite enlargement, karyotype 46, XY(X), PS++(15) are reported. A proband as well as his brother and sister suffered from phenotype with gradual hearing loss at the age of 12 to 13 and big satellite 15 existed in chromatinic karyotype. His father's phenotype was normal, but karyotype was the same as the 3 siblings of the proband, which suggested that the abnormal chromosome may originate from the father. The proband as well as his mother and uncle from family tree 2 may all suffer from dysaudia in both ears without any cause and with rapid exacerbation of the disease and deafness at last, 1 to 2 years after birth. Based on the fact that they had similar clinical phenotype and karyotype, their delayed deaf-mutism may be related to the structural abnormality of chromosome 15. An examination of the proband's grandparents showed that both phenotype and karyotype were normal. The abnormal chromosome from the proband's mother and uncle may originate from a new mutation. Obviously, the proband's abnormal chromosome originates from the mother. It is estimated that such chromosomal structural abnormality may be caused by some hearing genetic effects.

Adult↗
PubMed1993

Deletion of 19 base pairs in intron 13 of the gene for the pro alpha 2(I) chain of type-I procollagen (COL1A2) causes exon skipping in a proband with type-I osteogenesis imperfecta.

Skin fibroblasts from a proband with mild osteogenesis imperfecta (type I) synthesized normal pro alpha 2(I) chains and shortened pro alpha 2(I) chains of type-I procollagen. The type-I collagen that contained the shortened alpha 2(I) chains was thermally unstable in that it was cleaved at 30 degrees C by a mixture of trypsin and chymotrypsin. The mutation generating the shortened pro alpha 2(I) chains was shown to be a deletion of 19 base pairs from +4 to +22 of intron 13 of the COL1A2 gene by sequencing of genomic DNA and allele-specific oligonucleotide hybridization. The same mutation was found in the proband's affected father. Probe-protection experiments with S1 nuclease demonstrated that about 88% of the RNA transcripts from the mutated allele were spliced by exon skipping from exon 12 to exon 14 and that about 12% of the RNA transcripts were normally spliced. There was no evidence for use of cryptic splice sites, even though two cryptic splice sites had more favorable statistical scores and delta G degree 37 values than the new site that was created by the mutation and that was used for splicing of 12% of the transcripts into a normal mRNA. Comparison of the results with observations on 17 previously reported mutations that produced in-frame deletions of amino acids from the triple-helical domain of type-I collagen indicated that deletions in the N-terminal half of the alpha 2(I) chain tended to produce milder phenotypes than similar deletions elsewhere in the alpha 1(I) or alpha 2(I) chains.

Adolescent↗
PubMed1993

The association of leukocytes with secondary brain injury.

Shock increases mortality from brain injuries, but the mechanism is poorly understood. We hypothesized that brain injury followed by shock and resuscitation leads to a secondary reperfusion injury mediated in part by polymorphonuclear leukocytes (PMNs). To validate this hypothesis, we studied cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebral blood flow (CBF), cortical water content (CWC), and hemodynamic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock. Cerebral PMN accumulation (CPMN) in the injured and uninjured hemispheres was determined histologically from the total PMNs in five high-power fields (400x). Twenty-nine mature swine were randomized to four groups. Group 1, the control group, was instrumented only. Group 2 animals had a brain injury alone and were studied for 24 hours. Group 3 animals had a brain injury and hemorrhagic shock. Group 4 animals had hemorrhagic shock alone. Brain injury followed by shock caused a significantly greater ICP and a significantly lower CBF than brain injury or shock alone. There was no significant difference in CPP between groups after resuscitation. The CWC of the lesioned area was similar in both brain-injured groups but was significantly increased when compared with the controls and the shock-only group. The CWC of the nonlesioned hemisphere was higher in group 3 than in group 2. The CPMN in both hemispheres in group 3 was significantly greater than in either group 2 or group 4. There was a significant positive correlation between CPMN and both ICP and CWC, and a significant negative correlation between CPMN and CBF. These data suggest an association between CPMN accumulation and secondary brain injury.

Animals↗
PubMed1993

Effect of lesion volume on cerebral hemodynamics after focal brain injury and shock.

Cerebral blood flow (CBF) varies unpredictably in patients after head injury and hemorrhagic shock. Proper treatment requires knowledge of ischemic versus hyperemic flow. The degree to which the size or severity of the injury may contribute to CBF abnormalities is unknown. We hypothesized that lesion size is a determinant of postinjury CBF. We measured cerebral and systemic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock over a 5-hour period. Swine were randomized to receive either a large or small lesion followed by hemorrhage. In the small lesion group traumatic brain injury, followed by shock and resuscitation, produced a significant and sustained elevation in bihemispheric regional CBF and cerebral oxygen delivery that was significantly greater than that observed in either the large lesion group or the controls (p < 0.05). There were no significant differences between the experimental groups in volume of hemorrhage, intracranial pressure, cerebral perfusion pressure, arterial oxygen content, or PaCO2. These data suggest that the volume of injured tissue may determine post-resuscitation CBF, and that interventions to reduce cerebral blood volume (i.e., hyperventilation) may not be universally applicable in all head injured patients.

Animals↗
PubMed1993

Hypoxic ventilatory responsiveness in Tibetan compared with Han residents of 3,658 m.

Lifelong high-altitude residents of North and South America acquire blunted hypoxic ventilatory responses and exhibit decreased ventilation compared with acclimatized newcomers. The ventilatory characteristics of Himalayan high-altitude residents are of interest in the light of their reportedly lower hemoglobin levels and legendary exercise performance. Until recently, Sherpas have been the only Himalayan population available for study. To determine whether Tibetans exhibited levels of ventilation and hypoxic ventilatory drives that were as great as acclimatized newcomers, we compared 27 lifelong Tibetan residents of Lhasa, Tibet, China (3,658 m) with 30 acclimatized Han ("Chinese") newcomers matched for age, body size, and extent of exercise training. During room air breathing, minute ventilation was greater in the Tibetan than in the Han young men because of an increased respiratory frequency, but arterial O2 saturation and end-tidal PCO2 did not differ, indicating similar levels of effective alveolar ventilation. The Tibetan subjects had higher hypoxic ventilatory response shape parameter A values and hypercapnic ventilatory responsiveness than the Han subjects. Among the Han subjects, duration of high-altitude residence correlated with the degree of blunting of the hypoxic ventilatory drive. Paradoxically, hyperoxia (inspired O2 fraction 0.70) increased minute ventilation and decreased end-tidal PCO2 in the Tibetan but not in the Han men. We concluded that lifelong Tibetan residents of high altitude neither hypoventilated nor exhibited blunted hypoxic ventilatory responses compared with acclimatized Han newcomers, suggesting that the effects of lifelong high-altitude residence on ventilation and ventilatory response to hypoxia differ in Tibetan compared with other high-altitude populations.

Adult↗
PubMed1993

Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m.

Elevated pulmonary arterial pressure in high-altitude residents may be a maladaptive response to chronic hypoxia. If so, well-adapted populations would be expected to have pulmonary arterial pressures that are similar to sea-level values. Five normal male 22-yr-old lifelong residents of > or = 3,600 m who were of Tibetan descent were studied in Lhasa (3,658 m) at rest and during near-maximal upright ergometer exercise. We found that resting mean pulmonary arterial pressure [15 +/- 1 (SE) mmHg] and pulmonary vascular resistance (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while subjects breathed a hypoxic gas mixture [arterial O2 pressure (PaO2) = 36 +/- 2 Torr]. Near-maximal exercise [87 +/- 13% maximal O2 uptake (VO2max)] increased cardiac output more than threefold to values of 18.3 +/- 1.2 l/min but did not elevate pulmonary vascular resistance. Breathing 100% O2 during near-maximal exercise did not reduce pulmonary arterial pressure or vascular resistance. We concluded that this small sample of healthy Tibetans with lifelong residence > or = 3,658 m had resting pulmonary arterial pressures that were normal by sea-level standards and exhibited minimal hypoxic pulmonary vasoconstriction, both at rest and during exercise. These findings are consistent with remarkable cardiac performance and high-altitude adaptation.

Adult↗
PubMed1993

Autonomic regulation of heart rate response to exercise in Tibetan and Han residents of Lhasa (3,658 m).

To test the hypothesis that native high-altitude residents have less beta-sympathetic and more parasympathetic tone than newcomers, we compared the effects of beta-sympathetic and parasympathetic blockade in 10 Tibetan and 9 Han acclimatized male residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Each subject was studied during cycle ergometer exercise at 70, 132, and 191 W after placebo (normal saline), beta-sympathetic (propranolol, 0.2 mg/kg iv), or parasympathetic (atropine, 0.04 mg/kg iv) blockade in random order on different days. At rest, the fall in resting heart rate with propranolol and the rise with atropine were equal in Tibetan and Han subjects. During exercise, the fall in heart rate with propranolol relative to placebo values was greater in the Han than in the Tibetan group, whereas the rise in heart rate with atropine was greater in the Tibetans. Propranolol or atropine administration did not change minute ventilation per unit O2 consumption in either group. At the highest level of exercise on the placebo day, the Tibetans achieved a higher work load and level of O2 consumption than the Han subjects. Propranolol or atropine reduced O2 consumption and work load similarly in the two groups at the highest exercise level. The results supported our hypothesis that native Tibetan residents of high altitude exhibit more para-sympathetic and less beta-sympathetic tone during exercise. Neither relatively greater parasympathetic nor less sympathetic activation appeared implicated in the greater exercise capacity of Tibetans compared with that of acclimatized newcomer residents of high altitude.

Adult↗
PubMed1993

Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms.

Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms.

Adult↗
PubMed1992

Hemorrhagic hypotension after brain injury causes an early and sustained reduction in cerebral oxygen delivery despite normalization of systemic oxygen delivery.

Morbidity and mortality are doubled when hemorrhagic hypotension (HEM) accompanies a traumatic brain injury (TBI). Hemorrhagic hypotension initiates a "secondary" injury (SI) that has been attributed to ischemia, but this has not been confirmed in the laboratory. All previous studies have been of relatively short duration (less than 6 hours), allowing insufficient time to study the pathophysiology of SI, since maximal intracranial pressure (ICP) elevations may occur 16 to 20 hours after injury. We hypothesized that HEM combined with TBI would reduce cerebral oxygen delivery (cO2del) and cerebral metabolic rate for oxygen (cMRO2) to a greater degree than would occur with TBI alone. In a porcine model of TBI and HEM we recorded systemic oxygen delivery (sO2del), ICP, cerebral blood flow (CBF), cO2del, cMRO2, brain oxygen extraction ratio (cO2ER), and cortical water content (CWC) over a 24-hour study period. Controls (n = 7) were instrumented only, group 1 (n = 14) received a focal cryogenic lesion only, group 2 (n = 21) received a cryogenic lesion plus hemorrhage to 50 mm Hg for 45 minutes. Animals were resuscitated with crystalloid solutions; shed blood in group 2 animals was returned after one hour. Hemorrhagic hypotension following TBI produced a significant and sustained reduction in cO2del associated with a lower cMRO2 and cO2ER, and higher ICP and CWC, than seen with lesion alone. This occurred despite adequate early restoration of sO2del. This confirms that cerebral ischemia is ongoing despite restoration of systemic hemodynamics.

Animals↗
PubMed1992

Focal brain injury results in severe cerebral ischemia despite maintenance of cerebral perfusion pressure.

Severe head injury often causes an increase in intracranial pressure (ICP) and decreases in cerebral blood flow (CBF) and cerebral oxygen delivery (CO2del). To determine if this reduction in CBF and CO2del would produce cerebral ischemia and if this reduction would be abrogated by maintaining global cerebral perfusion pressure (CPP), we studied CPP, ICP, CBF, CO2del, cerebral oxygen extraction ratio (CO2ER), and cortical water content (CWC) in a porcine model of focal cryogenic brain injury. Fifteen mature swine were randomized to two groups. The experimental group (n = 7) had a brain lesion and was studied for 24 hours. The control group (n = 8) was instrumented only. Cryogenic injury significantly increased ICP and decreased CBF and CO2del compared with controls. There were no significant differences in CPP between the groups for the entire experiment, and the CPP was well above the ischemic threshold. The CO2ER significantly increased in the first three hours after brain injury. However, CO2ER in experimental animals tended to decrease 12 hours after brain injury and was not significantly different from that in controls. Cryogenic injury significantly increased the CWC in the lesioned hemisphere. These data indicate that focal brain injury results in persistent ischemia despite the normalization of CPP, suggesting that a significant increase in cerebral vascular resistance (CVR) occurs after brain injury. We conclude that in addition to maintenance of CPP, intervention to reduce CVR may be important in the management of brain injury.

Animals↗
PubMed1992

The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries.

Prehospital or admission hypotension doubles the mortality for patients with severe head injury (SHI = Glasgow Coma Scale score less than or equal to 8). To our knowledge no study to date has determined the effects of intraoperative hypotension [IH: systolic blood pressure (SBP) less than 90 mm Hg] on outcome in patients with SHI. This study examined 53 patients who had SHI and required early surgical intervention (surgery within 72 hours of injury). All patients were initially normotensive on arrival. There were 17 patients (32%) who developed IH and 36 (68%) who remained normotensive throughout surgery. The mortality rate was 82% in the IH group and 25% in the normotensive group (p less than 0.001). The duration of IH was inversely correlated with Glasgow Outcome Scale using linear regression (R = -0.30; p = 0.02). Despite vigorous fluid resuscitation in the IH group, additional pharmacologic support was used in only 32%. These data suggest that IH is not uncommon after SHI (32%) and that it does have a significant effect on patient outcome.

Adult↗
PubMed1992

Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m).

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han ("Chinese") 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.

Adult↗
PubMed1992

Intravenous fluid tonicity: effect on intracranial pressure, cerebral blood flow, and cerebral oxygen delivery in focal brain injury.

An investigation into the role of intravenous fluid tonicity in determining intracranial pressure (ICP) after brain injury is described. The authors compare the results of infusion of a hypotonic fluid (Ringer's lactate, 270 mOsm/liter) to those of a hypertonic fluid (hypertonic sodium lactate, 500 mOsm/liter) in a porcine model of focal cryogenic brain injury. Hemodynamic parameters (ICP, regional cerebral blood flow (CBF), and oxygen delivery) and serum osmolarity were measured every 3 hours for 24 hours after injury. At sacrifice, the water content of the lesioned and nonlesioned cortex was determined by specific gravity. The cryogenic injury produced a significant increase in ICP and a significant decrease in CBF in all experimental groups. Maintenance infusion of hypertonic sodium lactate for 24 hours resulted in significantly lower ICP, higher CBF and oxygen delivery, and higher serum osmolarity than Ringer's lactate infusion. Cortical water content in the area of the lesion was similar in both groups, but in the uninjured hemisphere it was significantly lower in the hypertonic group. These data suggest that hypertonic maintenance fluid improves intracranial compliance by dehydrating uninjured cortex. Improved CBF in the hypertonic group may be due to dehydration of cerebrovascular endothelium and erythrocytes. By reducing ICP and improving CBF, hypertonic fluid administration may thus reduce secondary brain injury after head trauma.

Animals↗
PubMed1992

[The use of 6-flavor Rehmannia decoction with additives in the prevention of ototoxic deafness induced by gentamicin in guinea pigs].

The purpose of this study is to discuss the effects of the Chinese medicine six-flavor Rehmannia Decoction with additives on preventing deafness induced by gentamicin (GM) in guinea pig by means of testing the thresholds of Preyer's reflex (PR) cochlear microphonic potential (CM), action potential of the auditory nerve (N1) and scanning electron microscope of inner ear (SEM). The results showed that the medicine is effective in reducing the ototoxic effect of GM on inner ear.

Action Potentials↗
PubMed1991

A comparison of hypertonic to isotonic fluid in the resuscitation of brain injury and hemorrhagic shock.

We studied the early and late effects of hypertonic resuscitation (HR) on the injured brain using a porcine model of hemorrhagic shock and focal cryogenic brain injury. After shock, swine were randomly assigned to receive a bolus (4 cc/kg) of either Ringers lactate (RL) or 7.5% hypertonic saline in 6% Dextran 70, followed by either RL or hypertonic sodium lactate to restore mean arterial pressure to baseline. All animals were studied for 24 hr after the start of resuscitation. Bolus HR improved cerebral blood flow (CBF) with a lower intracranial pressure (ICP) than RL. Continued hypertonic resuscitation prolonged the period of improved CBF and low ICP. At 24 hr CBF had deteriorated in the region of injury in all study groups and in the uninjured hemisphere in swine receiving RL. These data suggest that rapid resuscitation without increasing ICP for up to 6 hr as seen with hypertonic fluid could conceivably allow adequate time for surgical evacuation of mass lesions and effectively prevent secondary brain injury. This work underscores the importance of prolonged periods of study when evaluating brain resuscitation from traumatic shock.

Animals↗
PubMed1991

Hypertonic fluid resuscitation improves cerebral oxygen delivery and reduces intracranial pressure after hemorrhagic shock.

Prospective clinical studies have shown that hypotension from hemorrhage contributes to increased morbidity and mortality in patients with traumatic brain injury. It is implied that poorer outcome is the result of secondary brain injury from impaired cerebral oxygen delivery (cO2del). We studied the early and late effects of hypertonic sodium lactate (HSL: 500 mOsm/L) resuscitation on mean arterial pressure (MAP), cardiac output (CO), systemic oxygen delivery (sO2del), cerebral perfusion pressure (CPP), intracranial pressure (ICP), cO2del, cerebral blood flow (CBF), serum osmolality, and cortical water content (CWC) in a porcine model of hemorrhagic shock. Swine were randomized to receive a bolus (4 mL/kg) of either lactated Ringer's solution (LR: 274 mOsm/L) or HSL after shock, followed by either LR or HSL to return MAP to baseline levels. Shed blood was returned 1 hour after resuscitation, and all animals were studied for 24 hours. Control animals were instrumented only. The HSL resuscitation significantly increased cO2del and CBF for 24 hours postresuscitation when compared with LR. The ICP in the HSL-treated animals was significantly lower throughout the postresuscitation phase when compared with the LR-treated animals (p less than 0.05). The CWC was significantly lower in the HSL-treated animals (p less than 0.05). We attribute these effects to hypertonic dehydration of both the brain parenchyma and the cerebrovascular endothelium. These data suggest that by decreasing ICP and improving cO2del after shock, HSL could decrease secondary brain injury when brain injury and shock occur together.

Animals↗