Hemorrhagic Shock In Dogs Research Articles

Treatment of dogs in hemorrhagic shock by intraosseous infusion of hypertonic saline and dextran.

Under isoflurane anesthesia, 50% of the calculated blood volume was removed from 11 dogs. After 30 minutes, five dogs were treated with hypertonic saline and dextran (HSD) (5 mL/kg) followed by isotonic saline solution (2 mL/kg) intraosseously. Six dogs (controls) received isotonic saline (7 mL/kg) intraosseously. All treatments were administered through the medullary cavity of the tibia over a 30-minute period. Cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, and blood gases were monitored for 4 hours. Cardiac output, mean arterial pressure, and circulating volume (indicated by packed cell volume and total protein) were significantly improved after administration of HSD. We conclude that intraosseous infusion of HSD is efficacious in treating hemorrhagic shock and believe the technique may prove to be useful in clinical situations when intravenous lines cannot be established rapidly.

Effects of pentoxifylline on hemodynamics, oxygen transport, and tissue metabolism in experimental, severe hemorrhagic shock

It is hypothesized that pentoxifylline may be beneficial during shock states by improving tissue oxygenation. To test this hypothesis, we examined the effect of pentoxifylline on hemodynamics, oxygen delivery (DO2), and tissue metabolism during severe hemorrhagic shock. We conducted a placebo-controlled, randomized trial using anesthetized, mechanically ventilated dogs in hemorrhagic shock maintained at a mean arterial pressure of 45 to 50 mm Hg. Six animals were treated with a 10-mg/kg bolus of iv pentoxifylline followed by a continuous infusion at 5 mg/kg.hr. The controls consisted of six animals treated with saline. There were no significant differences between the groups before treatment. During 150 mins of posttreatment, repeated measurements of the control and pentoxifylline groups showed no significant differences in heart rate (HR), cardiac output, systemic and pulmonary vascular resistances, DO2, or blood lactate concentration (repeated-measures analysis of variance). In this acute, nonresuscitated, canine hemorrhagic shock model, pentoxifylline did not act as a vasodilator, or have any significant effect on HR, cardiac output, oxygen transport, or lactic acidosis.

Hypertonic/Hyperoncotic Fluid Resuscitation After Hemorrhagic Shock in Dogs

We compared canine systemic and cerebral hemodynamics after resuscitation from hemorrhagic shock with 4 mL/kg (a volume approximating 12% of shed blood volume) of 7.2% saline (HS; 1233 mEq/L sodium), 20% hydroxyethyl starch (HES) in 0.8% saline, or a combination fluid consisting of 20% hydroxyethyl starch in 7.2% saline (HS/HES). Eighteen endotracheally intubated mongrel dogs (18-24 kg) were ventilated to maintain normocarbia with 0.5% halothane in nitrous oxide and oxygen (60:40). After a 30-min period of hemorrhagic shock (mean arterial blood pressure = 40 mm Hg), extending from time T0 to T30, animals received one of three randomly assigned intravenous resuscitation fluids: HS, HES, or HS/HES. Data were collected at baseline, at the beginning and end of the shock period (T0 and T30), immediately after fluid infusion (T35), and at 60-min intervals for 2 h (T95, T155). After resuscitation, mean arterial blood pressure and cardiac output increased similarly in all groups, but failed to return to baseline. Intracranial pressure decreased during shock and increased slightly, immediately after resuscitation in all groups. During shock, cerebral blood flow (cerebral venous outflow method) declined in all groups. After resuscitation, cerebral blood flow increased, exceeding baseline in the HS and HS/HES groups but remaining low in the HES group (P less than 0.05 HS vs HES at T35). We conclude that small-volume resuscitation (4 mL/kg) with HS, HS/HES, or HES does not effectively restore or sustain systemic hemodynamics in hemorrhaged dogs. In dogs without intracranial pathology, the effects on cerebral hemodynamics are also comparable, except for transiently greater cerebral blood flow in the HS group in comparison with the HES group.

Resuscitation fluids for the treatment of hemorrhagic shock in dogs

The efficacy of using colloids vs. crystalloids in the treatment of hemorrhagic shock remains controversial. An important aspect in the treatment of hemorrhagic shock is the reestablishment of normal myocardial blood flow after fluid resuscitation. This study, therefore, was designed to investigate the effect of resuscitation with different plasma substitutes on myocardial blood flow and oxygen transport after acute hemorrhage in dogs. Forty-three dogs were anesthetized and bled into a heparinized Wiggers' reservoir to a mean arterial pressure of 35 mm Hg. The animals were maintained at this level of hypotension for 90 mins, whereupon the animals were infused with one of five randomly selected fluids: a) succinylated gelatin (Gelofusine); b) urea-linked gelatin (Haemaccel); c) 6% hetastarch (Hespan); d) lactated Ringer's solution; or e) shed blood. Myocardial blood flow was measured using the radiolabeled microsphere technique. Resuscitation with succinylated gelatin, urea-linked gelatin, and hetastarch resulted in significant hemodilution. However, infusion of these fluids resulted in a compensatory hyperemia that increased myocardial blood flow and maintained oxygen transport at preshock values. No hyperemia was observed with reinfusion of shed blood. Resuscitation with lactated Ringer's solution produced significant hemodilution without hyperemia and, consequently, a significant decrease in oxygen transport. These results suggest that in lieu of blood, the artificial colloids are more effective than crystalloids in restoring myocardial blood flow and oxygen transport after acute experimental hemorrhage in dogs.

Small-volume resuscitation from hemorrhagic shock in dogs

This study compared canine systemic hemodynamics and organ blood flow (radioactive microsphere technique) after resuscitation with 0.8% saline (Na+ 137 mEq/L), 7.2% hypertonic saline (Na+ 1233 mEq/L), 20% hydroxyethyl starch in 0.8% saline, or 20% hydroxyethyl starch in 7.2% saline, each in a volume approximating 15% of shed blood volume. Twenty-four endotracheally intubated mongrel dogs (18 to 24 kg) underwent a 30-min period of hemorrhagic shock, from time 0 to 30 min into the shock period, followed by fluid resuscitation. Data were collected at baseline, 15 min into the shock period, immediately after fluid infusion, 5 min after the beginning of resuscitation, and at 60-min intervals for 2 hr, (65 min after the beginning of resuscitation, and 125 min after the beginning of resuscitation). The animals received one of four randomly assigned iv resuscitation fluids: saline (54 mL/kg), hypertonic saline (6.0 mL/kg), hydroxyethel starch (6.0 mL/kg) or hypertonic saline/hydroxyethyl starch (6.0 mL/kg). Mean arterial pressure increased in all groups after resuscitation. Cardiac output increased with resuscitation in all groups, exceeding baseline in the saline and hypertonic saline/hydroxyethyl starch groups (p less than .05 compared with hypertonic saline or hydroxyethyl starch). Sixty-five minutes after the beginning of resuscitation, cardiac output was significantly (p less than .05) greater in either of the two colloid-containing groups than in the hypertonic saline group. After resuscitation, hypertonic saline and hydroxyethyl starch produced minimal improvements in hepatic arterial flow, hypertonic saline/hydroxyethyl starch increased hepatic arterial flow to near baseline levels, and saline markedly increased hepatic arterial flow to levels exceeding baseline (p less than .05, saline vs. hydroxyethyl starch). One hundred twenty-five minutes after the beginning of resuscitation, hepatic arterial flow had decreased in all groups; hepatic arterial flow in the hypertonic saline group had decreased to levels comparable with those during shock. Myocardial, renal, and brain blood flow were not significantly different between groups. Small-volume resuscitation with the combination of hypertonic saline/hydroxyethyl starch is comparable with much larger volumes of 0.8% saline, and is equal to hypertonic saline or hydroxyethyl starch in the ability to restore and sustain BP and improve organ blood flow after resuscitation from hemorrhagic shock.

Beneficial Effect of Upper Thoracic Epidural Anesthesia in Experimental Hemorrhagic Shock in Dogs

The question as to whether reduction of plasma catecholamine concentration contributes to the beneficial effects of upper thoracic epidural anesthesia on survival during hemorrhagic shock was examined. Twenty-six dogs were anesthetized with halothane and nitrous oxide, and blood was withdrawn to reduce the mean arterial blood pressure (MAP) to 40 mmHg. The 12 dogs in group A received both upper thoracic epidural anesthesia before the hemorrhage and intravenous infusion of epinephrine (450 ng.kg-1.min-1) and norepinephrine (150 ng.kg-1.min-1) during hemorrhage. The 14 dogs in group B received none of these. At 20 min after the start of the bleeding, plasma catecholamine concentrations were increased in both groups more than ten-fold. There were no significant intergroup differences with respect to these concentrations at any point during the experimental period. During the 100-min period of hemorrhage, 1 of the 12 animals in group A and 10 of the 14 in group B died. A significant difference in survival was seen between the two groups over the 100-min hypotensive period (P less than 0.01 by the generalized Wilcoxon test). These results suggest that the survival benefit of upper thoracic epidural anesthesia cannot be explained simply by differences in the level of catecholamines in the plasma, and that perhaps differences in the level of catecholamines at the nerve endings or other factors may be more important.

Protective effects of dopexamine hydrochloride in renal failure after acute haemorrhage in anaesthetized dogs

1. The present studies are designed to investigate whether dopexamine hydrochloride, a DA-1 receptor and beta 2-adrenoceptor agonist, is effective in preventing renal failure in Wiggers model of haemorrhagic shock in dogs. 2. Pentobarbital anaesthetized dogs were allowed to bleed into a reservoir and a hypotensive state (40-50 mmHg) was maintained for 120 min; subsequently blood was reinfused and recoveries in renal blood flow (RBF) and in various parameters reflecting renal function were monitored for an additional 150 min. 3. In the vehicle treated control group, despite a 45% recovery in the RBF, renal function was totally impaired. In the dopexamine treated groups, 80% recovery in RBF was accompanied by 60-120% recoveries in various indices of renal function such as GFR, UV, UNaV, after reinfusion of the shed blood. These salutary effects of DPX were dose dependent and were abolished by a selective DA-1 antagonist, SCH 23390. 4. These data suggest that the renal vasodilatory, natriuretic and diuretic effects of dopexamine and its ability to restore renal function after haemorrhagic shock are due to a direct action on the renal vascular and tubular DA-1 receptors. These studies demonstrate potential therapeutic usefulness of this agent in preventing renal failure.

Renal failure in haemorrhagic shock in dogs: Salutary effects of the calcium entry blocker felodipine

The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40-45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mumol/kg i.v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mumol/kg i.v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80-95% recovery in the renal blood flow, 60-65% in the glomerular filtration rate, 150-300% in the urine volume and 80-100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion. The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function.

Endotracheal epinephrine is unreliable

When intravenous access cannot be obtained in an emergency, the endotracheal route of emergency drug administration can be used for epinephrine, atropine, and lidocaine. Optimal drug dosages for endotracheal administration as well as the amount and type of diluent are presently unknown. We compared central intravenous, peripheral intravenous, intraosseous, and intratracheal administration of epinephrine 1:10,000 in both normotensive and hemorrhagic shock dogs. The shock model consisted of 50% blood volume depletion over 15 min. Epinephrine was administered in a dose of 0.01 mg/kg (0.1 cc/kg) by the intraosseous route, central, and peripheral intravenous routes followed by a 5 cc normal saline flush. Intratracheal administration consisted of epinephrine 0.01 and 0.02 mg/kg diluted 1:1 and 1:2 with normal saline or sterile water and administered deep into the tracheo-bronchial tree using a 30-cm catheter. The effect of epinephrine was assessed by the response of the arterial blood pressure. Epinephrine was equally effective by the intraosseous, central intravenous, and peripheral intravenous routes in terms of time to onset of action, time to peak effect, and magnitude of effect on systolic, diastolic, and mean arterial pressures in both the shock and non-shock animals. The duration of effect was significantly longer (P less than 0.02) for the intraosseous route of administration. The endotracheal route of administration was unreliable and not reproducible in either the normotensive or shock animals. In 8/12 episodes in normotensive animals, including 5 trials with double doses of 0.02 mg/kg and dilutions of 1:1 and 1:2, and in 4/9 studies with shock animals including three with double doses, there was no discernable response of systolic or diastolic blood pressure.

Effects of epidural anesthesia on cardiovascular response and survival in experimental hemorrhagic shock in dogs.

The purpose of the present study was to assess the effects of epidural anesthesia on cardiovascular responses and survival in experimental hemorrhagic shock in dogs. Thirty mongrel dogs were randomly assigned to one of three groups on the basis of anesthetic technique: the upper-level group (n = 10), receiving general anesthesia plus upper-level (mainly thoracic region) epidural anesthesia; the lower-level group (n = 10), receiving general anesthesia plus lower-level (mainly lumbar region) epidural anesthesia; and the control group (n = 10), receiving general anesthesia alone. After withdrawal of blood, the changes in mean arterial pressure (40 mmHg) and cardiac index were similar in all groups. In the upper-level group, a lower heart rate and systemic vascular resistance than the control group were maintained throughout in the presence of severe hypotension. A significant difference in survival was seen between the upper-level and control groups over the 100-min observation period as a whole (P less than 0.05 by the Generalized Wilcoxon test), since, at the end of the period, only two of the ten animals in the control group survived, whereas nine of ten in the upper-level group survived (P less than 0.001 by the Kaplan-Meier test). This result demonstrates that, in dogs lightly anesthetized with halothane and nitrous oxide, upper thoracic level epidural anesthesia significantly improves survival in experimental hemorrhagic shock (compared with survival in dogs with lumbar epidural or no epidural anesthesia) when the epidural is performed before hemorrhage and when the mean arterial pressure is constant.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of calcium-blocking agents on sympathetic responses to acute haemorrhagic shock in dogs

The effects of three calcium channel-blocking agents, verapamil, nifedipine and diltiazem, given intravenously, have been studied on the cardiovascular and sympathetic responses to acute haemorrhagic shock in anaesthetized dogs. Following acute haemorrhage, cardiac output, mean pulmonary artery pressure, mean right atrial pressure, and pulmonary capillary wedge pressure all fell, and adrenaline, noradrenaline and plasma renin activity rose. In the presence of each calcium antagonist the fall in cardiac output, mean pulmonary artery pressure, central venous pressure and pulmonary capillary wedge pressure was similar, and the rise in catecholamine levels unaffected. The rise in plasma renin activity following diltiazem 0.02 mg kg-1 or 0.1 mg kg-1 or nifedipine 0.01 mg kg-1 was similar to values in a control group, whereas in those receiving verapamil 0.15 mg kg-1 or 0.6 mg kg-1, or nifedipine 0.05 mg kg-1, the rise was greater.

Hypertonic and Hyperoncotic Resuscitation from Severe Hemorrhagic Shock in Dogs

Hypertonic and Hyperoncotic Resuscitation from Severe Hemorrhagic Shock in Dogs

Hypertonic and hyperoncotic resuscitation from severe hemorrhagic shock in dogs

Single bolus injections of hypertonic (7.5%) NaCl (H), hyperoncotic (6%) dextran-70 (D), or of their combination (HD) were given to severely bled (54.2 +/- 1.3 ml/kg) anesthetized dogs. Two shock procedures (30 or 60 min at 35 mm Hg) were tested. Survival was highest (11/12) after HD, lower (9/12) after H, and lowest (7/12) after D; it was higher (15/18 vs. 12/18) after the shorter vs. longer shock procedure. Cardiac index (CI) was restored to 83%-104% of prehemorrhage levels immediately after HD or H; 3 h later it was down to 67%-71% of control; after D, CI was stable at 41% to 50% of control; no differences in the relative performances of the agents tested in the 30 or 60-min shock durations. Arterial pressure recovered to near control levels in all groups; consequently, systemic vascular resistance was reduced after H and HD, but increased after D. Plasma volume recovered to 95% of control after H, 105% of control after HD, but only to 80% after D; however, the response to H was transient. Metabolic acidosis was partially reverted by all solutions. Plasma Na+ was transiently raised by H and HD. Overall differences detected between H vs. HD tend to favor HD as a resuscitative solution.

Protection by desferrioxamine against histopathological changes of the liver in the post-oligaemic phase of clinical haemorrhagic shock in dogs: correlation with improved survival rate and recovery.

Haemorrhagic shock was produced in anaesthetized dogs, by rapid arterial bleeding to mean arterial blood pressure 35 mmHg, and maintained oligaemic for 4 h followed by return of withdrawn blood(ROWB). Dogs were observed for 72 h after ROWB for survival and recovery, and, for histopathological (HP) studies on liver, dogs were sacrificed 2 h after ROWB in non-survival experiments. Desferrioxamine mesylate (25 mg/kg) was administered intra-muscularly at 2,3 and 4 h after blood loss in survival experiments and for HP studies the drug was given at 4 h in one group and at 2 h plus 4 h after blood loss in the second group. With the drug given at 3 or 4 h, survival was 70% and 100% while in the 2 h and the untreated groups it was 50%. Recovery was rapid in all the drug treated survivors, few became conscious within 30 min, showed slight activity by 4-6 h, all were almost normally active by 24 and fully so by 72 h after ROWB. All the 5 control survivors remained unconscious/drowsy upto 24 h; 3 were sluggish at 72 h. By group analysis, serum iron elevation during the oligaemic and at the end of the post-oligaemic phase was less in the drug-treated animals. HP changes of shock in the liver studied by light microscopy, were markedly reduced in severity and were less prevalent in the drug-treated dogs. The salutory effects of desferrioxamine may be due to inhibition of iron catalyzed free-radical production and tissue damage, through its strong iron chelating action. It may have a therapeutic advantage in this emergency condition without the disadvantages of toxicity inherent in prolonged use.

Effects of vasopressors on renal tissue gas tensions during hemorrhagic shock in dogs.

Effects of dopamine, epinephrine, and norepinephrine on renal tissue gas tension changes during hemorrhagic shock in dogs were investigated. The changes in the renal tissue gas tension were determined by the use of a Teflon membrane mass spectrometer. The animals were bled to a mean arterial pressure (MAP) of 50 mm Hg and maintained for one hour. Then, vasopressors were administered to maintain the MAP above 100 mm Hg. After the infusion of dopamine, the renal tissue oxygen tension (PrO2) was elevated for 20 min and tissue CO2 tension (PrCO2) decreased for 70 min. Neither PrO2 nor PrCO2 returned to the control levels. When epinephrine was infused, there was an initial slight transient rise in PrO2, which decreased gradually while PrCO2 decreased for 30 min and then gradually rose. When norepinephrine was infused, there was also an initial slight transient elevation in PrO2 which then decreased, while PrCO2 decreased transiently and then rose rapidly. These results suggest that although dopamine was the most useful vasopressor for improving renal tissue gas exchange during hemorrhagic shock, it did not restore completely oxygen delivery.

Role of central nervous system in renal nerve activity during prolonged hemorrhagic shock in dogs.

The contribution of sympathetic efferent outflow through the central nervous system (CNS) during prolonged hemorrhagic hypotension of 50 mmHg was examined in anesthetized dogs. Mean blood pressure, heart rate, and renal nerve activity (RNA) were recorded simultaneously after arterial bleeding for 2 h. In animals with an intact neuraxis, hemorrhage to approximately 50 mmHg increased RNA to 180 +/- 12% of control level at 5 min after bleeding, but returned close to control level after 10 min. A secondary increase in RNA followed, with its maximum (280 +/- 12%) at 30 min after bleeding. Then RNA gradually decreased so that at end of experiment (120 min after bleeding) RNA was 10 +/- 9% of control. The initial increase in RNA was abolished by denervation of afferents from carotid sinus and cardiopulmonary regions, but secondary RNA response during hemorrhagic hypotension was similar to that in the intact group and occurred when the head region of animals was exposed to a hypotension of 50 mmHg, and perfusion to peripheral regions of the body was maintained near normal range. However, when perfusion to the head was maintained at a steady level and peripheral regions were exposed to hypotension of 50 mmHg, RNA response did not change significantly. These results provide evidence that prolonged hemorrhagic hypotension, which induces severe brain ischemia, causes biphasic sympathetic outflow via the CNS. The increase in sympathetic activity was followed by decrease with time. This decrease may contribute to the pathogenesis of vasomotor paralysis occurring at the irreversible stage of hemorrhagic shock.

Pyridoxalated Polymerized Stroma-Free Hemoglobin Solution (SFHS-PP) as an Oxygen-Carrying Fluid Replacement for Hemorrhagic Shock in Dogs

Pyridoxalated Polymerized Stroma-Free Hemoglobin Solution (SFHS-PP) as an Oxygen-Carrying Fluid Replacement for Hemorrhagic Shock in Dogs

Hemodinamics, prolactin and catecholamines levels during hemorrhagic shock in dogs pretreated with a prolactin inhibitor (bromocriptine)

Bromocriptine, a dopaminomimetic drug, causing inhibition of prolactin secretion, was used in experiments on haemorrhagic shock in dogs. 5 dogs were treated with bromocriptine (0.4mg.day −1) for two days; a further 5 dogs were used as control animals. 30% of the blood volume was drawn from each dog. Mean arterial blood pressure, heart rate, central venous pressure, acid-base status, prolactin, GH and catecholamine levels were checked before blood letting and monitored until 1 hour after blood letting. Animals treated with bromocriptine showed a significant decrease of the mean arterial blood pressure and of the prolactin rate and a significant increase of catecholamine levels.

Prevention of fatal hemorrhagic shock in dog by pretreatment with chronic high-salt diet.

The ability of a chronic high-salt diet to prevent fatal hemorrhagic shock was examined in 36 mongrel dogs. Twenty-one dogs received a dietary supplement of 9 g sodium chloride/day for 6 wk, and 15 dogs received the same basic diet for 6 wk but without the sodium chloride supplement. Hemorrhagic shock was induced in all dogs by bleeding into an overhanging sealed reservoir. After 3 h of shock, salt-pretreated dogs had a lower systemic vascular resistance of 0.70 +/- 0.02 versus 1.44 +/- 0.04 mmHg X ml-1 X min X kg (P less than 0.01) and a higher cardiac output of 53 +/- 3 versus 26 +/- 3 ml X min-1 X kg-1 (P less than 0.01) than was observed in controls. At 2.5 h of shock, the salt-pretreated dogs also experienced an increase in gastrointestinal (P less than 0.01), hepatic arterial, (P less than 0.05), kidney (P less than 0.05), brain (P less than 0.01), and heart blood flows (P less than 0.001) compared with 0.5 h of shock, whereas the control dogs experienced no increased flow during this same period. We also observed that after 3 h of hypotension there was a significantly smaller increase in plasma renin activity in the salt-pretreated dogs. Administration of 0.1 U X kg-1 X min-1 of hog renin eliminated the differences in systemic vascular resistance, cardiac output, and survival in five salt-pretreated dogs.

Renal hypoxia and lactate metabolism in hemorrhagic shock in dogs.

Central and renal hemodynamics, renal cortical and medullary oxygen tension, and renal lactate metabolism were investigated in hemorrhagic shock in dogs. During graded hemorrhage, renal tissue PO2 decreased in parallel with renal blood flow, whereas renal lactate uptake remained virtually unchanged. During shock, below a mean arterial pressure (MAP) of 72 mm Hg, renal lactate utilization declined in parallel with tissue PO2. Renal lactate was produced at an MAP of 38 mm Hg. Reinfusion of shed blood increased renal tissue PO2 above its preshock value but did not restore baseline renal oxygen consumption and lactate uptake levels. These results suggest that renal lactate utilization is not limited by oxygen delivery under moderate hemorrhagic hypotension but decreases linearly with renal tissue PO2 during shock.